https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Shannon+King 2026-09-22T12:57:29Z User contributions MediaWiki 1.43.8 https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1062000 2010-03-29T00:59:56Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> {{STRUCTURE_1n4k | PDB=1n4k | SCENE= }}<br /> <br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type 1 InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;ref name=&quot;mainpaper&quot;/&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The InsP&lt;sub&gt;3&lt;/sub&gt;R protein does not belong to a superfamily of proteins. The receptor is thought to span the membrane 6 times, leaving the C-terminus in the cytoplasm.&lt;ref name=&quot;functionref&quot;/&gt; <br /> <br /> [[Image:1n4k1.PNG|left|thumb|An alternate view of the inositol 1,4,5-trisphosphate receptor highlighting the two domains and the binding site.]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> [[Image:1n4k2.png|thumb|The two domains of the inositol 1,4,5-trisphosphate receptor protein. The yellow ribbons represent the β-domain and the red helices represent the α-domain]]<br /> <br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand: Mechanism and Structural Components===<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt; &lt;scene name='Sandbox_170/1n4k/8'&gt;ligand&lt;/scene&gt; sits between the two domains of the protein. Highly basic amino acid residues are present on both domains and are responsible for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; Since the InsP&lt;sub&gt;3&lt;/sub&gt; ligand is highly charged, it is very likely to interact with the positively charged amino acids present in the N-terminus InsP&lt;sub&gt;3&lt;/sub&gt;-binding domain.&lt;ref name=&quot;functionref&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in InsP&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt; In all likelihood, the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site has been found to be made up of multiple sequences present throughout the N-terminal area of the protein.&lt;ref name=&quot;functionref&quot;/&gt; This makes the tertiary structure of the protein and proper folding absolutely integral to the function: if the protein does not fold correctly, then the multiple sequences of the protein making up the binding region cannot come together to be at all functional in binding the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of receptor activity ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; The stimulatory activity of ATP likely occurs through consensus adenine nucleotide-binding motifs.&lt;ref name=&quot;functionref&quot;/&gt; The inhibitory effect of ATP is thought to arise through its charged nature, acting as a competitive antagonist at the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt;R protein can autophosphorylate itself and is a substrate for multiple protein kinases.&lt;ref name=&quot;functionref&quot;/&gt; These kinases include cyclic AMP-dependent protein kinase (PKA), cyclic GMP-dependent protein kinase (PKG) and others.&lt;ref name=&quot;functionref&quot;/&gt; The protein kinases are thought to interact with the InsP&lt;sub&gt;3&lt;/sub&gt; receptor by controlling the sensitivity to Ca&lt;sup&gt;2+&lt;/sup&gt; in different tissues as well as affecting the sensitivity of InsP&lt;sub&gt;3&lt;/sub&gt; itself to Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=File:1n4k2.png&diff=1061999 2010-03-29T00:56:07Z

<p>Shannon King: </p> <hr /> <div></div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1061926 2010-03-28T19:11:50Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> {{STRUCTURE_1n4k | PDB=1n4k | SCENE= }}<br /> <br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type 1 InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;ref name=&quot;mainpaper&quot;/&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The InsP&lt;sub&gt;3&lt;/sub&gt;R protein does not belong to a superfamily of proteins. The receptor is thought to span the membrane 6 times, leaving the C-terminus in the cytoplasm.&lt;ref name=&quot;functionref&quot;/&gt; <br /> <br /> [[Image:1n4k1.PNG|left|thumb|An alternate view of the inositol 1,4,5-trisphosphate receptor highlighting the two domains and the binding site.]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> <br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand: Mechanism and Structural Components===<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt; &lt;scene name='Sandbox_170/1n4k/8'&gt;ligand&lt;/scene&gt; sits between the two domains of the protein. Highly basic amino acid residues are present on both domains and are responsible for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; Since the InsP&lt;sub&gt;3&lt;/sub&gt; ligand is highly charged, it is very likely to interact with the positively charged amino acids present in the N-terminus InsP&lt;sub&gt;3&lt;/sub&gt;-binding domain.&lt;ref name=&quot;functionref&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in InsP&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt; In all likelihood, the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site has been found to be made up of multiple sequences present throughout the N-terminal area of the protein.&lt;ref name=&quot;functionref&quot;/&gt; This makes the tertiary structure of the protein and proper folding absolutely integral to the function: if the protein does not fold correctly, then the multiple sequences of the protein making up the binding region cannot come together to be at all functional in binding the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of receptor activity ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; The stimulatory activity of ATP likely occurs through consensus adenine nucleotide-binding motifs.&lt;ref name=&quot;functionref&quot;/&gt; The inhibitory effect of ATP is thought to arise through its charged nature, acting as a competitive antagonist at the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt;R protein can autophosphorylate itself and is a substrate for multiple protein kinases.&lt;ref name=&quot;functionref&quot;/&gt; These kinases include cyclic AMP-dependent protein kinase (PKA), cyclic GMP-dependent protein kinase (PKG) and others.&lt;ref name=&quot;functionref&quot;/&gt; The protein kinases are thought to interact with the InsP&lt;sub&gt;3&lt;/sub&gt; receptor by controlling the sensitivity to Ca&lt;sup&gt;2+&lt;/sup&gt; in different tissues as well as affecting the sensitivity of InsP&lt;sub&gt;3&lt;/sub&gt; itself to Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1061547 2010-03-26T21:44:33Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> {{STRUCTURE_1n4k | PDB=1n4k | SCENE= }}<br /> <br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type 1 InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The InsP&lt;sub&gt;3&lt;/sub&gt;R protein does not belong to a superfamily of proteins. The receptor is thought to span the membrane 6 times, leaving the C-terminus in the cytoplasm.&lt;ref name=&quot;functionref&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> The above image also shows the two domains coming together to make the L-shaped structure.<br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> <br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand: Mechanism and Structural Components===<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt; &lt;scene name='Sandbox_170/1n4k/8'&gt;ligand&lt;/scene&gt; sits between the two domains of the protein. Highly basic amino acid residues are present on both domains and are responsible for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; Since the InsP&lt;sub&gt;3&lt;/sub&gt; ligand is highly charged, it is very likely to interact with the positively charged amino acids present in the N-terminus InsP&lt;sub&gt;3&lt;/sub&gt;-binding domain.&lt;ref name=&quot;functionref&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt; In all likelihood, the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site has been found to be made up of multiple sequences present throughout the N-terminal area of the protein.&lt;ref name=&quot;functionref&quot;/&gt; This makes the tertiary structure of the protein and proper folding absolutely integral to the function: if the protein does not fold correctly, then the multiple sequences of the protein making up the binding region cannot come together to be at all functional in binding the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of receptor activity ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;&lt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; The stimulatory activity of ATP likely occurs through consensus adenine nucleotide-binding motifs.&lt;ref name=&quot;functionref&quot;/&gt; The inhibitory effect of ATP is thought to arise through its charged nature, acting as a competitive antagonist at the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt;R protein can autophosphorylate itself and is a substrate for multiple protein kinases.&lt;ref name=&quot;functionref&quot;/&gt; These kinases include cyclic AMP-dependent protein kinase (PKA), cyclic GMP-dependent protein kinase (PKG) and others.&lt;ref name=&quot;functionref&quot;/&gt; The protein kinases are thought to interact with the InsP&lt;sub&gt;3&lt;/sub&gt; receptor by controlling the sensitivity to Ca&lt;sup&gt;2+&lt;/sup&gt; in different tissues as well as affecting the sensitivity of InsP&lt;sub&gt;3&lt;/sub&gt; itself to Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1060657 2010-03-24T19:25:44Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> {{STRUCTURE_1n4k | PDB=1n4k | SCENE= }}<br /> <br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type 1 InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The InsP&lt;sub&gt;3&lt;/sub&gt;R protein does not belong to a superfamily of proteins. The receptor is thought to span the membrane 6 times, leaving the C-terminus in the cytoplasm.&lt;ref name=&quot;functionref&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeats.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand: Mechanism and Structural Components===<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt; &lt;scene name='Sandbox_170/1n4k/8'&gt;ligand&lt;/scene&gt; sits between the two domains of the protein. Highly basic amino acid residues are present on both domains and are responsible for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; Since the InsP&lt;sub&gt;3&lt;/sub&gt; ligand is highly charged, it is very likely to interact with the positively charged amino acids present in the N-terminus InsP&lt;sub&gt;3&lt;/sub&gt;-binding domain.&lt;ref name=&quot;functionref&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt; In all likelihood, the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site has been found to be made up of multiple sequences present throughout the N-terminal area of the protein.&lt;ref name=&quot;functionref&quot;/&gt; This makes the tertiary structure of the protein and proper folding absolutely integral to the function: if the protein does not fold correctly, then the multiple sequences of the protein making up the binding region cannot come together to be at all functional in binding the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of receptor activity ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;&lt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; The stimulatory activity of ATP likely occurs through consensus adenine nucleotide-binding motifs.&lt;ref name=&quot;functionref&quot;/&gt; The inhibitory effect of ATP is thought to arise through its charged nature, acting as a competitive antagonist at the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt;R protein can autophosphorylate itself and is a substrate for multiple protein kinases.&lt;ref name=&quot;functionref&quot;/&gt; These kinases include cyclic AMP-dependent protein kinase (PKA), cyclic GMP-dependent protein kinase (PKG) and others.&lt;ref name=&quot;functionref&quot;/&gt; The protein kinases are thought to interact with the InsP&lt;sub&gt;3&lt;/sub&gt; receptor by controlling the sensitivity to Ca&lt;sup&gt;2+&lt;/sup&gt; in different tissues as well as affecting the sensitivity of InsP&lt;sub&gt;3&lt;/sub&gt; itself to Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1060654 2010-03-24T19:18:09Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> {{STRUCTURE_1n4k | PDB=1n4k | SCENE= }}<br /> <br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type 1 InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The InsP&lt;sub&gt;3&lt;/sub&gt;R protein does not belong to a superfamily of proteins. The receptor is thought to span the membrane 6 times, leaving the C-terminus in the cytoplasm.&lt;ref name=&quot;functionref&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeats.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand: Mechanism and Structural Components===<br /> <br /> The insP&lt;sub&gt;3&lt;/sub&gt; &lt;scene name='Sandbox_170/1n4k/8'&gt;ligand&lt;/scene&gt; sits between the two domains of the protein. Highly basic amino acid residues are present on both domains and are responsible for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; Since the InsP&lt;sub&gt;3&lt;/sub&gt; ligand is highly charged, it is very likely to interact with the positively charged amino acids present in the N-terminus InsP&lt;sub&gt;3&lt;/sub&gt;-binding domain.&lt;ref name=&quot;functionref&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt; In all likelihood, the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site has been found to be made up of multiple sequences present throughout the N-terminal area of the protein.&lt;ref name=&quot;functionref&quot;/&gt; This makes the tertiary structure of the protein and proper folding absolutely integral to the function: if the protein does not fold correctly, then the multiple sequences of the protein making up the binding region cannot come together to be at all functional in binding the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of receptor activity ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;&lt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; The stimulatory activity of ATP likely occurs through consensus adenine nucleotide-binding motifs.&lt;ref name=&quot;functionref&quot;/&gt; The inhibitory effect of ATP is thought to arise through its charged nature, acting as a competitive antagonist at the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt;R protein can autophosphorylate itself and is a substrate for multiple protein kinases.&lt;ref name=&quot;functionref&quot;/&gt; These kinases include cyclic AMP-dependent protein kinase (PKA), cyclic GMP-dependent protein kinase (PKG) and others.&lt;ref name=&quot;functionref&quot;/&gt; The protein kinases are thought to interact with the InsP&lt;sub&gt;3&lt;/sub&gt; receptor by controlling the sensitivity to Ca&lt;sup&gt;2+&lt;/sup&gt; in different tissues as well as affecting the sensitivity of InsP&lt;sub&gt;3&lt;/sub&gt; itself to Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1060649 2010-03-24T19:01:36Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> {{STRUCTURE_1n4k | PDB=1n4k | SCENE= }}<br /> <br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type 1 InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The InsP&lt;sub&gt;3&lt;/sub&gt;R protein does not belong to a superfamily of proteins. The receptor is thought to span the membrane 6 times, leaving the C-terminus in the cytoplasm.&lt;ref name=&quot;functionref&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeats.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand: Mechanism and Structural Components===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsible for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; Since the InsP&lt;sub&gt;3&lt;/sub&gt; ligand is highly charged, it is very likely to interact with the positively charged amino acids present in the N-terminus InsP&lt;sub&gt;3&lt;/sub&gt;-binding domain.&lt;ref name=&quot;functionref&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt; In all likelihood, the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site has been found to be made up of multiple sequences present throughout the N-terminal area of the protein.&lt;ref name=&quot;functionref&quot;/&gt; This makes the tertiary structure of the protein and proper folding absolutely integral to the function: if the protein does not fold correctly, then the multiple sequences of the protein making up the binding region cannot come together to be at all functional in binding the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of receptor activity ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;&lt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; The stimulatory activity of ATP likely occurs through consensus adenine nucleotide-binding motifs.&lt;ref name=&quot;functionref&quot;/&gt; The inhibitory effect of ATP is thought to arise through its charged nature, acting as a competitive antagonist at the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt;R protein can autophosphorylate itself and is a substrate for multiple protein kinases.&lt;ref name=&quot;functionref&quot;/&gt; These kinases include cyclic AMP-dependent protein kinase (PKA), cyclic GMP-dependent protein kinase (PKG) and others.&lt;ref name=&quot;functionref&quot;/&gt; The protein kinases are thought to interact with the InsP&lt;sub&gt;3&lt;/sub&gt; receptor by controlling the sensitivity to Ca&lt;sup&gt;2+&lt;/sup&gt; in different tissues as well as affecting the sensitivity of InsP&lt;sub&gt;3&lt;/sub&gt; itself to Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1059139 2010-03-23T17:46:58Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> '''Inositol 1,4,5-trisphosphate receptor protein'''<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor protein' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type 1 InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The InsP&lt;sub&gt;3&lt;/sub&gt;R protein does not belong to a superfamily of proteins. The receptor is thought to span the membrane 6 times, leaving the C-terminus in the cytoplasm.&lt;ref name=&quot;functionref&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeats.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand: Mechanism and Structural Components===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsible for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; Since the InsP&lt;sub&gt;3&lt;/sub&gt; ligand is highly charged, it is very likely to interact with the positively charged amino acids present in the N-terminus InsP&lt;sub&gt;3&lt;/sub&gt;-binding domain.&lt;ref name=&quot;functionref&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt; In all likelihood, the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site has been found to be made up of multiple sequences present throughout the N-terminal area of the protein.&lt;ref name=&quot;functionref&quot;/&gt; This makes the tertiary structure of the protein and proper folding absolutely integral to the function: if the protein does not fold correctly, then the multiple sequences of the protein making up the binding region cannot come together to be at all functional in binding the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of receptor activity ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;&lt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; The stimulatory activity of ATP likely occurs through consensus adenine nucleotide-binding motifs.&lt;ref name=&quot;functionref&quot;/&gt; The inhibitory effect of ATP is thought to arise through its charged nature, acting as a competitive antagonist at the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt;R protein can autophosphorylate itself and is a substrate for multiple protein kinases.&lt;ref name=&quot;functionref&quot;/&gt; These kinases include cyclic AMP-dependent protein kinase (PKA), cyclic GMP-dependent protein kinase (PKG) and others.&lt;ref name=&quot;functionref&quot;/&gt; The protein kinases are thought to interact with the InsP&lt;sub&gt;3&lt;/sub&gt; receptor by controlling the sensitivity to Ca&lt;sup&gt;2+&lt;/sup&gt; in different tissues as well as affecting the sensitivity of InsP&lt;sub&gt;3&lt;/sub&gt; itself to Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1059138 2010-03-23T17:45:53Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> '''Inositol 1,4,5-trisphosphate receptor protein'''<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor protein' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type 1 InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The InsP&lt;sub&gt;3&lt;/sub&gt;R protein does not belong to a superfamily of proteins. The receptor is thought to span the membrane 6 times, leaving the C-terminus in the cytoplasm.&lt;ref name=&quot;functionref&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeats.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand: Mechanism and Structural Components===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsible for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; Since the InsP&lt;sub&gt;3&lt;/sub&gt; ligand is highly charged, it is very likely to interact with the positively charged amino acids present in the N-terminus InsP&lt;sub&gt;3&lt;/sub&gt;-binding domain.&lt;ref name=&quot;functionref&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt; In all likelihood, the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site has been found to be made up of multiple sequences present throughout the N-terminal area of the protein.&lt;ref name=&quot;functionref&quot;/&gt; This makes the tertiary structure of the protein and proper folding absolutely integral to the function: if the protein does not fold correctly, then the multiple sequences of the protein making up the binding region cannot come together to be at all functional in binding the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of receptor activity ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;&lt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; The stimulatory activity of ATP likely occurs through consensus adenine nucleotide-binding motifs.&lt;ref name=&quot;functionref&quot;/&gt; The inhibitory effect of ATP is thought to arise through its charged nature, acting as a competitive antagonist at the InsP&lt;sub&gt;3&lt;/sub&gt;-binding site.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt;R protein can autophosphorylate itself and is a substrate for multiple protein kinases.&lt;ref name=&quot;functionref&quot;/&gt; These kinases include cyclic AMP-dependent protein kinase (PKA), cyclic GMP-dependent protein kinase (PKG) and others.&lt;ref name=&quot;functionref&quot;/&gt; The protein kinases are thought to interact with the InsP&lt;sub&gt;3&lt;/sub&gt; receptor by controlling the sensitivity to Ca&lt;sup&gt;2+&lt;/sup&gt; in different tissues as well as affecting the sensitivity of InsP&lt;sub&gt;3&lt;/sub&gt; itself to Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> == Mechanism ==<br /> <br /> The mechanism of the Ins&lt;sub&gt;3&lt;/sub&gt; protein has been mentioned, but this section will describe it in more detail. <br /> <br /> <br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1059137 2010-03-23T17:33:38Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> '''Inositol 1,4,5-trisphosphate receptor protein'''<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor protein' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type 1 InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The InsP&lt;sub&gt;3&lt;/sub&gt;R protein does not belong to a superfamily of proteins. The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeats.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of receptor activity ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;&lt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; The stimulatory activity of ATP likely occurs through consensus adenine nucleotide-binding motifs.&lt;ref name=&quot;functionref&quot;/&gt; The inhibitory effect of ATP is thought to arise through its charged nature, acting as a competitive antagonist at the IP&lt;sub&gt;3&lt;/sub&gt;-binding site.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt;R protein can autophosphorylate itself and is a substrate for multiple protein kinases.&lt;ref name=&quot;functionref&quot;/&gt; These kinases include cyclic AMP-dependent protein kinase (PKA), cyclic GMP-dependent protein kinase (PKG) and others.&lt;ref name=&quot;functionref&quot;/&gt; The protein kinases are thought to interact with the InsP&lt;sub&gt;3&lt;/sub&gt; receptor by controlling the sensitivity to Ca&lt;sup&gt;2+&lt;/sup&gt; in different tissues as well as affecting the sensitivity of IP&lt;sub&gt;3&lt;/sub&gt; itself to Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1059136 2010-03-23T17:31:40Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> '''Inositol 1,4,5-trisphosphate receptor protein'''<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor protein' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type 1 InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The InsP&lt;sub&gt;3&lt;/sub&gt;R protein does not belong to a superfamily of proteins. The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeats.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of receptor activity ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;&lt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; The binding sites responsible for such activity are likely consensus adenine-nucleotide-binding motifsInositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type 1 InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The InsP&lt;sub&gt;3&lt;/sub&gt;R protein does not belong to a superfamily of proteins. The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeats.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of receptor activity ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;&lt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; The stimulatory activity of ATP likely occurs through consensus adenine nucleotide-binding motifs.&lt;ref name=&quot;functionref&quot;/&gt; The inhibitory effect of ATP is thought to arise through its charged nature, acting as a competitive antagonist at the IP&lt;sub&gt;3&lt;/sub&gt;-binding site.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> The InsP&lt;sub&gt;3&lt;/sub&gt;R protein can autophosphorylate itself and is a substrate for multiple protein kinases.&lt;ref name=&quot;functionref&quot;/&gt; These kinases include cyclic AMP-dependent protein kinase (PKA), cyclic GMP-dependent protein kinase (PKG) and others.&lt;ref name=&quot;functionref&quot;/&gt; The protein kinases are thought to interact with the InsP&lt;sub&gt;3&lt;/sub&gt; receptor by controlling the sensitivity to Ca&lt;sup&gt;2+&lt;/sup&gt; in different tissues as well as affecting the sensitivity of IP&lt;sub&gt;3&lt;/sub&gt; itself to Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1058088 2010-03-19T04:12:04Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> '''Inositol 1,4,5-trisphosphate receptor protein'''<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Insert caption here' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeats.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of receptor activity ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;&lt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1058084 2010-03-19T03:31:44Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represents the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeats.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of the receptor ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;&lt;2+&lt;/sup&gt;. Increased ATP concentrations increase receptor activity whereas higher concentrations decrease receptor activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1058083 2010-03-19T03:29:01Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represents the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeats.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation of the receptor ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;/sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> The method of regulation by ATP on the receptor is very similar to that of Ca&lt;sup&gt;&lt;2+&lt;/sup&gt;<br /> <br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1058082 2010-03-19T03:22:41Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represents the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeats.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> === Regulation ===<br /> <br /> Sequences within the receptor protein have been found to interact with accessory proteins. Additionally, there are sites for ATP binding and for phosphorylation.&lt;ref name=&quot;functionref&quot;/&gt; All of these interactions would play a role in the regulation of the InsP&lt;sub&gt;3&lt;/sub&gt; receptor protein.<br /> <br /> A very important property of the receptor is that it is regulated by Ca&lt;sup&gt;2+&lt;/sup&gt; concentrations. Lower concentrations make the receptor more sensitive to InsP&lt;sub&gt;3&lt;/sub&gt; while high concentrations can inhibit the receptor activity.&lt;ref name=&quot;functionref&quot;/&gt; Also, the receptor itself can bind Ca&lt;sup&gt;3&lt;/sup&gt; itself at more than one site. A Ca&lt;sup&gt;2+&lt;/sup&gt; binding site within the ligand binding domain may even suggest that these Ca&lt;sup&gt;2+&lt;/sup&gt; binding sites are involved in the effects Ca&lt;sup&gt;2+&lt;sup&gt; has on InsP&lt;sub&gt;3&lt;/sub&gt; binding to its ligand.<br /> <br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1058080 2010-03-19T03:05:36Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represent the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeat.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> === Role in Ca&lt;sup&gt;2+&lt;/sup&gt; regulation ===<br /> <br /> The presence of inositol 1,4,5-trisphosphate functions to increase the cytosolic concentration of Ca&lt;sup&gt;2+&lt;/sup&gt;.&lt;ref name=&quot;functionref&quot;&gt;PMID:10378086&lt;/ref&gt; The InsP&lt;sub&gt;3&lt;/sub&gt; is formed at the plasma membrane, diffuses into the cytosol, and binds to the InsP&lt;sub&gt;3&lt;/sub&gt; receptor which is found in the membrane of intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; stores.&lt;ref name=&quot;functionref&quot;/&gt; The release of Ca&lt;sup&gt;2+&lt;/sup&gt; can propagate to other cells and can help to coordinate the functionality of organ systems.&lt;ref name=&quot;functionref&quot;/&gt; Areas of the body rich in the InsP&lt;sub&gt;3&lt;/sub&gt; receptor are the cerebellum and, more specifically, the endoplasmic reticulum, and even the plasma membrane and nuclei of some tissues.&lt;ref name=&quot;functionref&quot;/&gt; Recent results also suggest that InsP&lt;sub&gt;3&lt;/sub&gt; receptors work in intrinsic Ca&lt;sup&gt;2+&lt;/sup&gt; channel activity.&lt;ref name=&quot;functionref&quot;/&gt;<br /> <br /> <br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1058009 2010-03-19T00:52:04Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represent the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is from Bosanac et al.'s 2002 paper &quot;Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.&quot;&lt;ref name=&quot;mainpaper&quot;/&gt; This image shows a cartoon representation of both the β-trefoil and α-domain armadillo repeat.<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1058005 2010-03-19T00:47:42Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represent the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; <br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> The above image is<br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG| thumb|Inositol 1,4,5-trisphosphate]]<br /> <br /> <br /> <br /> <br /> == Function ==<br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1057992 2010-03-19T00:07:04Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represent the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;PMID:12442173&lt;/ref&gt;<br /> <br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;ref name=&quot;mainpaper&quot;/&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;ref name=&quot;mainpaper&quot;/&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;ref name=&quot;mainpaper&quot;/&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;ref name=&quot;mainpaper&quot;/&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor.&lt;ref name=&quot;mainpaper&quot;/&gt; In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;ref name=&quot;mainpaper&quot;/&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;ref name=&quot;mainpaper&quot;/&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;ref name=&quot;mainpaper&quot;/&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;ref name=&quot;mainpaper&quot;/&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;ref name=&quot;mainpaper&quot;/&gt; The structures of the two domains can be seen in the image below.<br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;ref name=&quot;mainpaper&quot;/&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;ref name=&quot;mainpaper&quot;/&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;ref name=&quot;mainpaper&quot;/&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;ref name=&quot;mainpaper&quot;/&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;ref name=&quot;mainpaper&quot;/&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG]]<br /> <br /> A representation of the InsP&lt;sub&gt;3&lt;/sub&gt;R ligand, InsP&lt;sub&gt;3&lt;/sub&gt;<br /> <br /> <br /> == Function ==<br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1057988 2010-03-18T23:52:46Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represent the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;ref name=&quot;mainpaper&quot;&gt;Bosanac I, Allatia JR, Mal TK, Chan J, Talarico S, Tong, FK, Tong KI, Yoshikawa, F, Furuichi T, Iwai M, Michikawa, T, Mikoshiba, Ikura M. Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand. Nature. 2002 Dec 12;420(6916):&lt;696-700 PMID:12442173./ref&gt;<br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;sup&gt;1&lt;/sup&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;sup&gt;[1]&lt;/sup&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;sup&gt;[1]&lt;/sup&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor. In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;sup&gt;[1]&lt;/sup&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;sup&gt;[1]&lt;/sup&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;sup&gt;[1]&lt;/sup&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;sup&gt;[1]&lt;/sup&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;sup&gt;[1]&lt;/sup&gt; The structures of the two domains can be seen in the image below.<br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;sup&gt;[1]&lt;/sup&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;sup&gt;[1]&lt;/sup&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;sup&gt;[1]&lt;/sup&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;sup&gt;[1]&lt;/sup&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG]]<br /> <br /> A representation of the InsP&lt;sub&gt;3&lt;/sub&gt;R ligand, InsP&lt;sub&gt;3&lt;/sub&gt;<br /> <br /> <br /> == Function ==<br /> <br /> ==References== <br /> <br /> &lt;references /&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1057875 2010-03-18T00:25:14Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represent the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;sup&gt;[1]&lt;/sup&gt;<br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;sup&gt;1&lt;/sup&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;sup&gt;[1]&lt;/sup&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;sup&gt;[1]&lt;/sup&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor. In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;sup&gt;[1]&lt;/sup&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;sup&gt;[1]&lt;/sup&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;sup&gt;[1]&lt;/sup&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;sup&gt;[1]&lt;/sup&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;sup&gt;[1]&lt;/sup&gt; The structures of the two domains can be seen in the image below.<br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;sup&gt;[1]&lt;/sup&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;sup&gt;[1]&lt;/sup&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;sup&gt;[1]&lt;/sup&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;sup&gt;[1]&lt;/sup&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG]]<br /> <br /> A representation of the InsP&lt;sub&gt;3&lt;/sub&gt;R ligand, InsP&lt;sub&gt;3&lt;/sub&gt;<br /> <br /> <br /> == Function ==<br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1057874 2010-03-18T00:23:47Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represent the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;sup&gt;[1]&lt;/sup&gt;<br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;sup&gt;1&lt;/sup&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;sup&gt;[1]&lt;/sup&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;sup&gt;[1]&lt;/sup&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor. In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;sup&gt;[1]&lt;/sup&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;sup&gt;[1]&lt;/sup&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;sup&gt;[1]&lt;/sup&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;sup&gt;[1]&lt;/sup&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;sup&gt;[1]&lt;/sup&gt; The structures of the two domains can be seen in the image below.<br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;sup&gt;[1]&lt;/sup&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;sup&gt;[1]&lt;/sup&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;sup&gt;[1]&lt;/sup&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;sup&gt;[1]&lt;/sup&gt;<br /> <br /> <br /> [[Image:Ligand1.PNG]]<br /> A representation of the InsP&lt;sub&gt;3&lt;/sub&gt;R ligand, InsP&lt;sub&gt;3&lt;/sub&gt;<br /> <br /> <br /> == Function ==<br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=File:Ligand1.PNG&diff=1057873 2010-03-18T00:22:21Z

<p>Shannon King: </p> <hr /> <div></div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1057868 2010-03-18T00:12:48Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represent the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;sup&gt;[1]&lt;/sup&gt;<br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;sup&gt;1&lt;/sup&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;sup&gt;[1]&lt;/sup&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;sup&gt;[1]&lt;/sup&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor. In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;sup&gt;[1]&lt;/sup&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;sup&gt;[1]&lt;/sup&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;sup&gt;[1]&lt;/sup&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;sup&gt;[1]&lt;/sup&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;sup&gt;[1]&lt;/sup&gt; The structures of the two domains can be seen in the image below.<br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;sup&gt;[1]&lt;/sup&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;sup&gt;[1]&lt;/sup&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;sup&gt;[1]&lt;/sup&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;sup&gt;[1]&lt;/sup&gt;<br /> <br /> == Function ==<br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1057866 2010-03-18T00:11:23Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represent the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;sup&gt;[1]&lt;/sup&gt;<br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;sup&gt;1&lt;/sup&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;sup&gt;[1]&lt;/sup&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;sup&gt;[1]&lt;/sup&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor. In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;sup&gt;[1]&lt;/sup&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;sup&gt;[1]&lt;/sup&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;sup&gt;[1]&lt;/sup&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;sup&gt;[1]&lt;/sup&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;sup&gt;[1]&lt;/sup&gt; The structures of the two domains can be seen in the image below.<br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;sup&gt;[1]&lt;/sup&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;sup&gt;[1]&lt;/sup&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain. The hydroxyl groups of InsP&lt;sub&gt;3&lt;/sub&gt; play a small role in binding to InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sub&gt; Additionally, 9 out of 12 Arg/Lys residues play a very important role in ligand binding and salt bridges to stabilize between the domain regions.&lt;sup&gt;[1]&lt;/sup&gt; The non-basic residues T266, T267, G268, and Y567 are also integral in Insp&lt;sub&gt;3&lt;/sub&gt; coordination: if T267, G268 or Y567 residues are mutated then there will be a significant reduction in ligand binding.&lt;sup&gt;[1]&lt;/sup&gt;<br /> <br /> == Function ==<br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1057828 2010-03-17T20:18:04Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represent the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;sup&gt;[1]&lt;/sup&gt;<br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;sup&gt;1&lt;/sup&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;sup&gt;[1]&lt;/sup&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;sup&gt;[1]&lt;/sup&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor. In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;sup&gt;[1]&lt;/sup&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;sup&gt;[1]&lt;/sup&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;sup&gt;[1]&lt;/sup&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;sup&gt;[1]&lt;/sup&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;sup&gt;[1]&lt;/sup&gt; The structures of the two domains can be seen in the image below.<br /> <br /> <br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> ----<br /> <br /> <br /> === Binding the InsP&lt;sub&gt;3&lt;/sub&gt; Ligand ===<br /> <br /> Highly basic amino acid residues are present on both domains and are responsile for the binding of InsP&lt;sub&gt;3&lt;/sub&gt; to InsP&lt;sub&gt;3&lt;/sub&gt;R.&lt;sup&gt;[1]&lt;/sup&gt; In binding, water molecules are involved in hydrogen bonding between InsP&lt;sub&gt;3&lt;/sub&gt; and its receptor as well as interactions between protein side chains and phosphorous.&lt;sup&gt;[1]&lt;/sup&gt; Coordination of phosphorous groups is mediated by residues in both the β-domain and α-domain.<br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1057825 2010-03-17T20:05:51Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor. The red and orange molecule represent the ligand of the protein, inositol 1,4,5-trisphosphate' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;sup&gt;[1]&lt;/sup&gt;<br /> == Overall Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;sup&gt;1&lt;/sup&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;sup&gt;[1]&lt;/sup&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> === Domain Structure ===<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;sup&gt;[1]&lt;/sup&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor. In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;sup&gt;[1]&lt;/sup&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;sup&gt;[1]&lt;/sup&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;sup&gt;[1]&lt;/sup&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;sup&gt;[1]&lt;/sup&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> The structures of the two domains can be seen in the image below.<br /> [[Image:fold regions.PNG]]<br /> <br /> <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1057822 2010-03-17T19:56:15Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/8'&gt;Inositol 1,4,5-trisphosphate receptor protein&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;sup&gt;[1]&lt;/sup&gt;<br /> == Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;sup&gt;1&lt;/sup&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;sup&gt;[1]&lt;/sup&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;sup&gt;[1]&lt;/sup&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor. In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;sup&gt;[1]&lt;/sup&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;sup&gt;[1]&lt;/sup&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;sup&gt;[1]&lt;/sup&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;sup&gt;[1]&lt;/sup&gt; A possible option for this kind of binding domain would be the InsP&lt;sub&gt;3&lt;/sub&gt; binding suppressor domain present at the N-terminus which reduces the binding affinity for the InsP&lt;sub&gt;3&lt;/sub&gt; ligand.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1057817 2010-03-17T19:19:03Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/4'&gt;Inositol 1,4,5-trisphosphate receptor&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;sup&gt;[1]&lt;/sup&gt;<br /> == Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;sup&gt;1&lt;/sup&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;sup&gt;[1]&lt;/sup&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt; The overall structure with the ligand bound can be seen here:<br /> <br /> [[Image:1n4k1.PNG]]<br /> <br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;sup&gt;[1]&lt;/sup&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor. In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;sup&gt;[1]&lt;/sup&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;sup&gt;[1]&lt;/sup&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;sup&gt;[1]&lt;/sup&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1057799 2010-03-17T18:47:19Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/4'&gt;Inositol 1,4,5-trisphosphate receptor&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-trisphosphate receptor' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;sup&gt;[1]&lt;/sup&gt;<br /> == Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R) protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;sup&gt;1&lt;/sup&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;sup&gt;[1]&lt;/sup&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt;<br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;sup&gt;[1]&lt;/sup&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor. In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;sup&gt;[1]&lt;/sup&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;sup&gt;[1]&lt;/sup&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;R1, there are two large, highly conserved surfaces.&lt;sup&gt;[1]&lt;/sup&gt; Both regions are rich in aromatic residues, indicating that they may function as interaction sites for parts of the receptor or other cellular proteins.&lt;sup&gt;[1]&lt;/sup&gt; <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1056174 2010-03-16T21:36:13Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/4'&gt;Inositol 1,4,5-trisphosphate receptor&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-triphosphate receptor' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;sup&gt;[1]&lt;/sup&gt;<br /> == Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R)protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;sup&gt;1&lt;/sup&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices, which come together to form a barrel.&lt;sup&gt;[1]&lt;/sup&gt; The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt;<br /> <br /> The protein fold of the β-domain can also be called the β-trefoil. This element is present in other proteins as well, including fibroblast growth factors and mannose receptors.&lt;sup&gt;[1]&lt;/sup&gt; In the case of the InsP&lt;sub&gt;3&lt;/sub&gt;R β-trefoil, the structure was found to be very similar to the β-trefoil of the mannose receptor. In the β-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R1, three of six two-stranded hairpins come together to form a barrel and the other three form a triangular cap for the barrel.&lt;sup&gt;[1]&lt;/sup&gt; <br /> <br /> The α-domain of InsP&lt;sub&gt;3&lt;/sub&gt;R shows a high degree of homology with an element called an armidillo repeat fold found in proteins such as β-catenin and importins.&lt;sup&gt;[1]&lt;/sup&gt; In β-catenin and importins, the armadillo repeat functions as a motif for protein-protein interactions.&lt;sup&gt;[1]&lt;/sup&gt; Within the α-domain of mouse InsP&lt;sub&gt;3&lt;/sub&gt;, <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1056173 2010-03-16T20:44:50Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/4'&gt;Inositol 1,4,5-trisphosphate receptor&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-triphosphate receptor' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;sup&gt;[1]&lt;/sup&gt;<br /> == Structure ==<br /> The specific type of inositol 1,4,5-trisphosphate receptor (InsP&lt;sub&gt;3&lt;/sub&gt;R)protein discussed here is the mouse type one InsP&lt;sub&gt;3&lt;/sub&gt;R, also called InsP&lt;sub&gt;3&lt;/sub&gt;R1. This polypeptide contains three major regions: the amino terminal inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;) binding region, the central modulatory region, and the carboxy-terminus channel region.&lt;sup&gt;1&lt;/sup&gt; The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices.&lt;sup&gt;[1]&lt;/sup&gt; These components form a barrel. The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for InsP&lt;sub&gt;3&lt;/sub&gt;.&lt;sup&gt;[1]&lt;/sup&gt;<br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1056171 2010-03-16T19:12:34Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/4'&gt;Inositol 1,4,5-triphosphate receptor&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-triphosphate receptor' /&gt;<br /> <br /> Inositol 1,4,5-trisphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms &lt;sup&gt;[1]&lt;/sup&gt;<br /> == Structure ==<br /> The protein forms an L-shaped structure composed of two asymmetric domains perpendicular to each other.&lt;sup&gt;[1]&lt;/sup&gt; The N-terminal domain is made up of 12 β-strands and 2 single-turn helices.&lt;sup&gt;[1]&lt;/sup&gt; These components form a barrel. The C-terminal end is quite different, consisting of a bundle made of eight α-helices.&lt;sup&gt;[1]&lt;/sup&gt; The interface of the two domains is lined with basic residues and forms the receptor site for inositol 1,4,5-trisphosphate (InsP&lt;sub&gt;3&lt;/sub&gt;).&lt;sup&gt;[1]&lt;/sup&gt;<br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1053874 2010-03-09T20:43:18Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/4'&gt;Inositol 1,4,5-triphosphate receptor&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-triphosphate receptor' /&gt;<br /> <br /> Inositol 1,4,5-triphosphate receptor binding protein is a ubiquitous protein involved in the Ca&lt;sup&gt;2+&lt;/sup&gt; signalling processes in a variety of organisms&lt;sup&gt;[1]&lt;/sup&gt;<br /> == Overview ==<br /> <br /> ----</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1053854 2010-03-09T19:39:14Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/4'&gt;Inositol 1,4,5-triphosphate receptor&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-triphosphate receptor' /&gt;<br /> <br /> == Overview ==</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1053853 2010-03-09T19:37:38Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/4'&gt;Inositol 1,4,5-triphosphate receptor&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-triphosphate receptor' /&gt;<br /> Inositol</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1053852 2010-03-09T19:24:15Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/4'&gt;Inositol 1,4,5-triphosphate receptor&lt;/scene&gt;<br /> &lt;applet load='1n4k' size='300' frame='true' align='right' caption='Inositol 1,4,5-triphosphate receptor' /&gt;</div>

Shannon King https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1053850 2010-03-09T19:17:58Z

<p>Shannon King: </p> <hr /> <div>&lt;table style=&quot;background-color:#ffffc0&quot; cellpadding=&quot;8&quot; width=&quot;95%&quot; border=&quot;0&quot;&gt;&lt;tr&gt;&lt;td&gt;Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].&lt;/td&gt;&lt;/tr&gt;<br /> Shannon King<br /> <br /> <br /> &lt;scene name='Sandbox_170/1n4k/4'&gt;Inositol 1,4,5-triphosphate receptor&lt;/scene&gt;</div>

Shannon King https://proteopedia.org/index.php?title=File:1N4K.pdb&diff=1053849 2010-03-09T19:07:20Z

<p>Shannon King: </p> <hr /> <div></div>

Shannon King