https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Jaclyn+Gordon 2026-09-14T22:06:36Z User contributions MediaWiki 1.43.8 https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1062541 2010-03-31T00:39:50Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependent protein degradation&lt;ref name=&quot;mainpaper&quot;&gt;PMID: 3041007&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin &lt;ref name=&quot;mainpaper&quot;/&gt;. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes&lt;ref name=&quot;mainpaper&quot;/&gt;.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well&lt;ref name=&quot;mainpaper&quot;/&gt;.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven lysine and four arginine residues&lt;ref name=&quot;2.8Aref&quot;&gt;PMID: 2987935&lt;/ref&gt;. Many aspects of ubiquitin's structure aids in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core&lt;ref name=&quot;mainpaper&quot;/&gt;. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus&lt;ref name=&quot;mainpaper&quot;/&gt;. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> Secondary structures found throughout ubiquitin include three and one half turns of α-helix, a short 3&lt;sub&gt;10&lt;/sub&gt; helix, a mixed β-sheet with five strands and seven reverse turns. Several unusual secondary structures are also seen including parallel G1 β-bulge, two reverse Asx turns and a symmetrical hydrogen-bonding region between two helices and two reverse turns.<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref name=&quot;2.8Aref&quot;/&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiquitin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group&lt;ref name=&quot;mainpaper&quot;/&gt;.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2, through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly&lt;ref name=&quot;mainpaper&quot;/&gt;.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]][[Image:Ubq_pathway.png| thumb |right | upright=2.0 |Ubiquitinylation pathway]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition&lt;ref name=&quot;mainpaper&quot;/&gt;.<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading will either inhibit or stimulate the ubiquitin-dependent process of protein degradation. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref name=&quot;Ubproteindeg&quot;&gt;PMID: 3022650&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal Gly76 of ubiquitin&lt;ref name=&quot;regulation&quot;&gt;PMID: 9409543&lt;/ref&gt;.<br /> [[Image:proteosome length.png| thumb |left | upright=0.75 |Length view of Proteasome]]<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome&lt;ref&gt;Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439&lt;/ref&gt;. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrade the fragments into their appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.<br /> <br /> =Types of Ubiquitin Conjugates=<br /> There are 3 different types of ubiquitin conjugates known:<br /> === Ubiquitinylation === <br /> Ubiquitinylation simply refers to the isopeptide bond formation between the carboxyl-terminal of ubiquitin and the ε-amino acid side chain of the target protein.<br /> === Multi-ubiquitinylation ===<br /> This type of ubiquitin conjugate is a critical step in the process of protein degradation. This process refers to the addition of single ubiquitin molecules to numerous lysine residues on a target protein.<br /> === Polyubiquitinylation === <br /> This conjugate formation is the most important process in protein degradation as it is believed to signal the protein for degradation. Polyubiquitinylation refers to the addition of several ubiquitin molecules to a single lysine residue on a protein. Isopeptide bonds are formed between the carboxyl-terminus of one ubiquitin and a lysine residue on an adjacent ubiquitin.<br /> =Diseases=<br /> There are numerous diseases that may develop as a result of ubiquitin abnormalities. There are two disease categories possible in non-lethal states. One being the result of function loss and the other being function gain. Loss of function may occur due to a target substrate mutation or a mutation in a ubiquitin enzyme causing protein stabilization and a decrease in protein degradation. Function gain, on the other hand, results in an increase in protein degradation. <br /> Cancer may result from either case. Oncoproteins may become stabilized while tumor suppressor genes may become destabilized. Liddle's Syndrome is a type of early-onset hypertension&lt;ref name=&quot;liddles&quot;&gt;PMID: 8521520&lt;/ref&gt;. Sodium ions and water are excessively reabsorbed caused by E3 ligase non-recognition. Angleman syndrome is caused by a E3 ligase defect. This defect causes affects in human brain development resulting in symptoms such as mental retardation, seizures and abnormal gait. Lastly, neurogenetive diseases are caused by the accumulation of ubiquitin-conjugates. Diseases of this nature include Alzheimers and Parkinson's.<br /> =References=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1062120 2010-03-29T17:56:55Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref name=&quot;mainpaper&quot;&gt;PMID: 3041007&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues&lt;ref name=&quot;2.8Aref&quot;&gt;PMID: 2987935&lt;/ref&gt;. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> Secondary structures found throughout ubiquitin include three and one half turns of α-helix, a short 3&lt;sub&gt;10&lt;/sub&gt; helix, a mixed β-sheet with five strands and seven reverse turns. Several unusual secondary structures are also seen including parallel G1 β-bulge, two reverse Asx turns and a symmetrical hydrogen-bonding region between two helices and two reverse turns.<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref name=&quot;2.8Aref&quot;/&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]][[Image:Ubq_pathway.png| thumb |right | upright=2.0 |Ubiquitinylation pathway]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> <br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref name=&quot;Ubproteindeg&quot;&gt;PMID: 3022650&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref name=&quot;regulation&quot;&gt;PMID: 9409543&lt;/ref&gt;.<br /> [[Image:proteosome length.png| thumb |left | upright=0.75 |Length view of Proteasome]]<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome&lt;ref&gt;Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439&lt;/ref&gt;. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.<br /> <br /> =Types of Ubiquitin Conjugates=<br /> There are 3 different types of ubiquitin conjugates known:<br /> === Ubiquitinylation === <br /> Ubiquitinylation simply refers to the isopeptide bond formations between the carboxyl-terminal of ubiquitin and the ε-amino acid side chain of the target proteins.<br /> === Multi-ubiquitinylation ===<br /> This type of ubiquitin conjugate is a critical step in the process of protein degradation. This process refers to the addition of single ubiquitin molecules to numerous lysine residues on a target protein.<br /> === Polyubiquitinylation === <br /> This conjugate formation is the most important process in protein degradation as it officially targets the protein for degradation. Polyubiquitinylation refers to the addition of several ubiquitin molecules to a single lysine residue on a protein. Isopeptide bonds are formed between the carboxyl-terminus of one ubiquitin and a lysine residue on an adjacent ubiquitin.<br /> =Diseases=<br /> There are numerous diseases that may develop as a result of ubiquitin abnormalities. There are two disease categories possible in non-lethal states. One being the result of function loss and the other being function gain. Loss of function may occur due to a target substrate mutation or a mutation in a ubiquitin enzyme causing protein stabilization and a decrease in protein degradation. Function gain, on the other hand, results in an increase in protein degradation. <br /> Cancer may result from either cases. Oncoproteins may become stabilized while tumor suppressor genes may become destabilized. Liddle's Syndrome is a type of early-onset hypertension&lt;ref name=&quot;liddles&quot;&gt;PMID: 8521520&lt;/ref&gt;. Sodium ions and water are excessively reabsorbed caused by E3 ligase non-recognition. Angleman syndrome is caused by a E3 ligase defect. This defect causes affects in human brain development resulting in symptoms such as mental retardation, seizures and abnormal gait. Lastly, neurogenetive diseases are caused by the accumulation of ubiquitin-conjugates. Diseases of this nature include Alzheimers and Parkinson's.<br /> =References=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1062052 2010-03-29T03:22:45Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref name=&quot;mainpaper&quot;&gt;PMID: 3041007&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues&lt;ref name=&quot;2.8Aref&quot;&gt;PMID: 2987935&lt;/ref&gt;. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> Secondary structures found throughout the ubiquitin structure include three and one half turns of α-helix, a short 3&lt;sub&gt;10&lt;/sub&gt; helix, a mixed β-sheet with five strands and seven reverse turns. Several unusual secondary structures are also seen including parallel G1 β-bulge, two reverse Asx turns and a symmetrical hydrogen-bonding region between two helices and two reverse turns.<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref name=&quot;2.8Aref&quot;/&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]][[Image:Ubq_pathway.png| thumb |right | upright=2.0 |Ubiquitinylation pathway]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> <br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref name=&quot;Ubproteindeg&quot;&gt;PMID: 3022650&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref name=&quot;regulation&quot;&gt;PMID: 9409543&lt;/ref&gt;.<br /> [[Image:proteosome length.png| thumb |left | upright=0.75 |Length view of Proteasome]]<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome&lt;ref&gt;Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439&lt;/ref&gt;. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.<br /> <br /> =Types of Ubiquitin Conjugates=<br /> There are 3 different types of ubiquitin conjugates known:<br /> === Ubiquitinylation === <br /> Ubiquitinylation simply refers to the isopeptide bond formations between the carboxyl-terminal of ubiquitin and the ε-amino acid side chain of the target proteins.<br /> === Multi-ubiquitinylation ===<br /> This type of ubiquitin conjugate is a critical step in the process of protein degradation. This process refers to the addition of single ubiquitin molecules to numerous lysine residues on a target protein.<br /> === Polyubiquitinylation === <br /> This conjugate formation is the most important process in protein degradation as it officially targets the protein for degradation. Polyubiquitinylation refers to the addition of several ubiquitin molecules to a single lysine residue on a protein. Isopeptide bonds are formed between the carboxyl-terminus of one ubiquitin and a lysine residue on an adjacent ubiquitin.<br /> =Diseases=<br /> There are numerous diseases that may develop as a result of ubiquitin abnormalities. There are two disease categories possible in non-lethal states. One being the result of function loss and the other being function gain. Loss of function may occur due to a target substrate mutation or a mutation in a ubiquitin enzyme causing protein stabilization and a decrease in protein degradation. Function gain, on the other hand, results in an increase in protein degradation. <br /> Cancer may result from either cases. Oncoproteins may become stabilized while tumor suppressor genes may become destabilized. Liddle's Syndrome is a type of early-onset hypertension&lt;ref name=&quot;liddles&quot;&gt;PMID: 8521520&lt;/ref&gt;. Sodium ions and water are excessively reabsorbed caused by E3 ligase non-recognition. Angleman syndrome is caused by a E3 ligase defect. This defect causes affects in human brain development resulting in symptoms such as mental retardation, seizures and abnormal gait. Lastly, neurogenetive diseases are caused by the accumulation of ubiquitin-conjugates. Diseases of this nature include Alzheimers and Parkinson's.<br /> =References=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1062051 2010-03-29T03:20:12Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref name=&quot;mainpaper&quot;&gt;PMID: 3041007&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues&lt;ref name=&quot;2.8Aref&quot;&gt;PMID: 2987935&lt;/ref&gt;. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> Secondary structures found throughout the ubiquitin structure include three and one half turns of α-helix, a short 3&lt;sub&gt;10&lt;/sub&gt; helix, a mixed β-sheet with five strands and seven reverse turns. Several unusual secondary structures are also seen including parallel G1 β-bulge, two reverse Asx turns and a symmetrical hydrogen-bonding region between two helices and two reverse turns.<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref name=&quot;2.8Aref&quot;/&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]][[Image:Ubq_pathway.png| thumb |right | upright=2.0 |Ubiquitinylation pathway]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> <br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref name=&quot;Ubproteindeg&quot;&gt;PMID: 3022650&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref name=&quot;regulation&quot;&gt;PMID: 9409543&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome&lt;ref&gt;Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439&lt;/ref&gt;. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.[[Image:proteosome length.png| thumb |none | upright=0.75 |Length view of Proteasome]]<br /> <br /> =Types of Ubiquitin Conjugates=<br /> There are 3 different types of ubiquitin conjugates known:<br /> === Ubiquitinylation === <br /> Ubiquitinylation simply refers to the isopeptide bond formations between the carboxyl-terminal of ubiquitin and the ε-amino acid side chain of the target proteins.<br /> === Multi-ubiquitinylation ===<br /> This type of ubiquitin conjugate is a critical step in the process of protein degradation. This process refers to the addition of single ubiquitin molecules to numerous lysine residues on a target protein.<br /> === Polyubiquitinylation === <br /> This conjugate formation is the most important process in protein degradation as it officially targets the protein for degradation. Polyubiquitinylation refers to the addition of several ubiquitin molecules to a single lysine residue on a protein. Isopeptide bonds are formed between the carboxyl-terminus of one ubiquitin and a lysine residue on an adjacent ubiquitin.<br /> =Diseases=<br /> There are numerous diseases that may develop as a result of ubiquitin abnormalities. There are two disease categories possible in non-lethal states. One being the result of function loss and the other being function gain. Loss of function may occur due to a target substrate mutation or a mutation in a ubiquitin enzyme causing protein stabilization and a decrease in protein degradation. Function gain, on the other hand, results in an increase in protein degradation. <br /> Cancer may result from either cases. Oncoproteins may become stabilized while tumor suppressor genes may become destabilized. Liddle's Syndrome is a type of early-onset hypertension&lt;ref name=&quot;liddles&quot;&gt;PMID: 8521520&lt;/ref&gt;. Sodium ions and water are excessively reabsorbed caused by E3 ligase non-recognition. Angleman syndrome is caused by a E3 ligase defect. This defect causes affects in human brain development resulting in symptoms such as mental retardation, seizures and abnormal gait. Lastly, neurogenetive diseases are caused by the accumulation of ubiquitin-conjugates. Diseases of this nature include Alzheimers and Parkinson's.<br /> =References=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1062047 2010-03-29T03:08:57Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref name=&quot;mainpaper&quot;&gt;PMID: 3041007&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues&lt;ref name=&quot;2.8Aref&quot;&gt;PMID: 2987935&lt;/ref&gt;. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> Secondary structures found throughout the ubiquitin structure include three and one half turns of α-helix, a short 3&lt;sub&gt;10&lt;/sub&gt; helix, a mixed β-sheet with five strands and seven reverse turns. Several unusual secondary structures are also seen including parallel G1 β-bulge, two reverse Asx turns and a symmetrical hydrogen-bonding region between two helices and two reverse turns.<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref name=&quot;2.8Aref&quot;/&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]][[Image:Ubq_pathway.png| thumb |right | upright=2.0 |Ubiquitinylation pathway]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> <br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref name=&quot;Ubproteindeg&quot;&gt;PMID: 3022650&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref name=&quot;regulation&quot;&gt;PMID: 9409543&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome&lt;ref&gt;Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439&lt;/ref&gt;. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.[[Image:proteosome length.png| thumb |none | upright=0.75 |Length view of Proteasome]][[Image:proteaosome top.png| thumb |left | upright=1.0 |Top view of proteasome]]<br /> <br /> =Types of Ubiquitin Conjugates=<br /> There are 3 different types of ubiquitin conjugates known:<br /> === Ubiquitinylation === <br /> Ubiquitinylation simply refers to the isopeptide bond formations between the carboxyl-terminal of ubiquitin and the ε-amino acid side chain of the target proteins.<br /> === Multi-ubiquitinylation ===<br /> This type of ubiquitin conjugate is a critical step in the process of protein degradation. This process refers to the addition of single ubiquitin molecules to numerous lysine residues on a target protein.<br /> === Polyubiquitinylation === <br /> This conjugate formation is the most important process in protein degradation as it officially targets the protein for degradation. Polyubiquitinylation refers to the addition of several ubiquitin molecules to a single lysine residue on a protein. Isopeptide bonds are formed between the carboxyl-terminus of one ubiquitin and a lysine residue on an adjacent ubiquitin.<br /> =Diseases=<br /> There are numerous diseases that may develop as a result of ubiquitin abnormalities. There are two disease categories possible in non-lethal states. One being the result of function loss and the other being function gain. Loss of function may occur due to a target substrate mutation or a mutation in a ubiquitin enzyme causing protein stabilization and a decrease in protein degradation. Function gain, on the other hand, results in an increase in protein degradation. <br /> Cancer may result from either cases. Oncoproteins may become stabilized while tumor suppressor genes may become destabilized. Liddle's Syndrome is a type of early-onset hypertension&lt;ref name=&quot;liddles&quot;&gt;PMID: 8521520&lt;/ref&gt;. Sodium ions and water are excessively reabsorbed caused by E3 ligase non-recognition. Angleman syndrome is caused by a E3 ligase defect. This defect causes affects in human brain development resulting in symptoms such as mental retardation, seizures and abnormal gait. Lastly, neurogenetive diseases are caused by the accumulation of ubiquitin-conjugates. Diseases of this nature include Alzheimers and Parkinson's.<br /> =References=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1062045 2010-03-29T02:53:30Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref name=&quot;mainpaper&quot;&gt;PMID: 3041007&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref name=&quot;2.8Aref&quot;&gt;PMID: 2987935&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]][[Image:Ubq_pathway.png| thumb |right | upright=2.0 |Ubiquitinylation pathway]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> <br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref name=&quot;Ubproteindeg&quot;&gt;PMID: 3022650&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref name=&quot;regulation&quot;&gt;PMID: 9409543&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome&lt;ref&gt;Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439&lt;/ref&gt;. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.[[Image:proteosome length.png| thumb |none | upright=0.75 |Length view of Proteasome]][[Image:proteaosome top.png| thumb |left | upright=1.0 |Top view of proteasome]]<br /> <br /> =Types of Ubiquitin Conjugates=<br /> There are 3 different types of ubiquitin conjugates known:<br /> === Ubiquitinylation === <br /> Ubiquitinylation simply refers to the isopeptide bond formations between the carboxyl-terminal of ubiquitin and the ε-amino acid side chain of the target proteins.<br /> === Multi-ubiquitinylation ===<br /> This type of ubiquitin conjugate is a critical step in the process of protein degradation. This process refers to the addition of single ubiquitin molecules to numerous lysine residues on a target protein.<br /> === Polyubiquitinylation === <br /> This conjugate formation is the most important process in protein degradation as it officially targets the protein for degradation. Polyubiquitinylation refers to the addition of several ubiquitin molecules to a single lysine residue on a protein. Isopeptide bonds are formed between the carboxyl-terminus of one ubiquitin and a lysine residue on an adjacent ubiquitin.<br /> =Diseases=<br /> There are numerous diseases that may develop as a result of ubiquitin abnormalities. There are two disease categories possible in non-lethal states. One being the result of function loss and the other being function gain. Loss of function may occur due to a target substrate mutation or a mutation in a ubiquitin enzyme causing protein stabilization and a decrease in protein degradation. Function gain, on the other hand, results in an increase in protein degradation. <br /> Cancer may result from either cases. Oncoproteins may become stabilized while tumor suppressor genes may become destabilized. Liddle's Syndrome is a type of early-onset hypertension&lt;ref name=&quot;liddles&quot;&gt;PMID: 8521520&lt;/ref&gt;. Sodium ions and water are excessively reabsorbed caused by E3 ligase non-recognition. Angleman syndrome is caused by a E3 ligase defect. This defect causes affects in human brain development resulting in symptoms such as mental retardation, seizures and abnormal gait. Lastly, neurogenetive diseases are caused by the accumulation of ubiquitin-conjugates. Diseases of this nature include Alzheimers and Parkinson's.<br /> =References=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1062043 2010-03-29T02:44:43Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref name=&quot;mainpaper&quot;&gt;PMID: 3041007&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref name=&quot;2.8Aref&quot;&gt;PMID: 2987935&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]][[Image:Ubq_pathway.png| thumb |right | upright=2.0 |Ubiquitinylation pathway]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> <br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref name=&quot;Ubproteindeg&quot;&gt;PMID: 3022650&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref name=&quot;regulation&quot;&gt;PMID: 9409543&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome&lt;ref&gt;Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439&lt;/ref&gt;. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.[[Image:proteosome length.png| thumb |none | upright=0.75 |Length view of Proteasome]][[Image:proteaosome top.png| thumb |left | upright=1.0 |Top view of proteasome]]<br /> <br /> =Types of Ubiquitin Conjugates=<br /> There are 3 different types of ubiquitin conjugates known:<br /> === Ubiquitinylation === <br /> Ubiquitinylation simply refers to the isopeptide bond formations between the carboxyl-terminal of ubiquitin and the ε-amino acid side chain of the target proteins.<br /> === Multi-ubiquitinylation ===<br /> This type of ubiquitin conjugate is a critical step in the process of protein degradation. This process refers to the addition of single ubiquitin molecules to numerous lysine residues on a target protein.<br /> === Polyubiquitinylation === <br /> This conjugate formation is the most important process in protein degradation as it officially targets the protein for degradation. Polyubiquitinylation refers to the addition of several ubiquitin molecules to a single lysine residue on a protein. Isopeptide bonds are formed between the carboxyl-terminus of one ubiquitin and a lysine residue on an adjacent ubiquitin.<br /> =Diseases=<br /> There are numerous diseases that may develop as a result of ubiquitin abnormalities. There are two disease categories possible in non-lethal states. One being the result of function loss and the other being function gain. Loss of function may occur due to a target substrate mutation or a mutation in a ubiquitin enzyme causing protein stabilization and a decrease in protein degradation. Function gain, on the other hand, results in an increase in protein degradation. <br /> Cancer may result from either cases. Oncoproteins may become stabilized while tumor suppressor genes may become destabilized. Liddle's Syndrome is a type of early-onset hypertension&lt;ref name=&quot;liddles&quot;&gt;PMID: 8521520&lt;/ref&gt;. Sodium ions and water are excessively reabsorbed caused by E3 ligase non-recognition.<br /> =References=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1062027 2010-03-29T02:08:20Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref name=&quot;mainpaper&quot;&gt;PMID: 3041007&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref name=&quot;2.8Aref&quot;&gt;PMID: 2987935&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]][[Image:Ubq_pathway.png| thumb |right | upright=2.0 |Ubiquitinylation pathway]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> <br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref name=&quot;Ubproteindeg&quot;&gt;PMID: 3022650&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref name=&quot;regulation&quot;&gt;PMID: 9409543&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome&lt;ref&gt;Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439&lt;/ref&gt;. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.[[Image:proteosome length.png| thumb |none | upright=0.75 |Length view of Proteasome]][[Image:proteaosome top.png| thumb |left | upright=1.0 |Top view of proteasome]]<br /> <br /> =Types of Ubiquitin Conjugates=<br /> There are 3 different types of ubiquitin conjugates known:<br /> === Ubiquitinylation === <br /> Ubiquitinylation simply refers to the isopeptide bond formations between the carboxyl-terminal of ubiquitin and the ε-amino acid side chain of the target proteins.<br /> === Multi-ubiquitinylation ===<br /> This type of ubiquitin conjugate is a critical step in the process of protein degradation. This process refers to the addition of single ubiquitin molecules to numerous lysine residues on a target protein.<br /> === Polyubiquitinylation === <br /> This conjugate formation is the most important process in protein degradation as it officially targets the protein for degradation. Polyubiquitinylation refers to the addition of several ubiquitin molecules to a single lysine residue on a protein. Isopeptide bonds are formed between the carboxyl-terminus of one ubiquitin and a lysine residue on an adjacent ubiquitin.<br /> =Diseases=<br /> There are numerous diseases that may develop as a result of ubiquitin abnormalities. <br /> =References=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1062024 2010-03-29T02:02:58Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref name=&quot;mainpaper&quot;&gt;PMID: 3041007&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref name=&quot;2.8Aref&quot;&gt;PMID: 2987935&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]][[Image:Ubq_pathway.png| thumb |right | upright=2.0 |Ubiquitinylation pathway]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> <br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref name=&quot;Ubproteindeg&quot;&gt;PMID: 3022650&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref name=&quot;regulation&quot;&gt;PMID: 9409543&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome&lt;ref&gt;Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439&lt;/ref&gt;. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.[[Image:proteosome length.png| thumb |none | upright=0.75 |Length view of Proteasome]][[Image:proteaosome top.png| thumb |left | upright=1.0 |Top view of proteasome]]<br /> <br /> =Types of Ubiquitin Conjugates=<br /> There are 3 different types of ubiquitin conjugates known:<br /> === Ubiquitinylation === <br /> Ubiquitinylation simply refers to the isopeptide bond formations between the carboxyl-terminal of ubiquitin and the ε-amino acid side chain of the target proteins.<br /> === Multi-ubiquitinylation ===<br /> This type of ubiquitin conjugate is a critical step in the process of protein degradation. This process refers to the addition of single ubiquitin molecules to numerous lysine residues on a target protein.<br /> === Polyubiquitinylation === <br /> This conjugate formation is the most important process in protein degradation as it officially targets the protein for degradation. Polyubiquitinylation refers to the addition of several ubiquitin molecules to a single lysine residue on a protein. Isopeptide bonds are formed between the carboxyl-terminus of one ubiquitin and a lysine residue on an adjacent ubiquitin.<br /> =Diseases=<br /> =References=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1062011 2010-03-29T01:40:50Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref name=&quot;mainpaper&quot;&gt;PMID: 3041007&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref name=&quot;2.8Aref&quot;&gt;PMID: 2987935&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> [[Image:Ubq_pathway.png| thumb |centre | upright=2.0 |Ubiquitinylation pathway]]<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref name=&quot;Ubproteindeg&quot;&gt;PMID: 3022650&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref name=&quot;regulation&quot;&gt;PMID: 9409543&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome&lt;ref&gt;Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439&lt;/ref&gt;. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.<br /> [[Image:proteosome length.png| thumb |left | upright=0.75 |Length view of Proteasome]]<br /> [[Image:proteaosome top.png| thumb |right | upright=1.0 |Top view of proteasome]]<br /> <br /> =Types of Ubiquitin Conjugates=<br /> There are 3 different types of ubiquitin conjugates known:<br /> === Ubiquitinylation === <br /> Ubiquitinylation simply refers to the isopeptide bond formations between the carboxyl-terminal of ubiquitin and the ε-amino acid side chain of the target proteins.<br /> === Multi-ubiquitinylation ===<br /> This type of ubiquitin conjugate is a critical step in the process of protein degradation. This process refers to the addition of single ubiquitin molecules to numerous lysine residues on a target protein.<br /> === Polyubiquitinylation === <br /> This conjugate formation is the most important process in protein degradation as it officially targets the protein for degradation. Polyubiquitinylation refers to the addition of several ubiquitin molecules to a single lysine residue on a protein. Isopeptide bonds are formed between the carboxyl-terminus of one ubiquitin and a lysine residue on an adjacent ubiquitin.<br /> =Diseases=<br /> =References=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1062003 2010-03-29T01:21:19Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref name=&quot;mainpaper&quot;&gt;PMID: 3041007&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref name=&quot;2.8Aref&quot;&gt;PMID: 2987935&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> [[Image:Ubq_pathway.png| thumb |centre | upright=2.0 |Ubiquitinylation pathway]]<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref name=&quot;Ubproteindeg&quot;&gt;PMID: 3022650&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref name=&quot;regulation&quot;&gt;PMID: 9409543&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome&lt;ref&gt;Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439&lt;/ref&gt;. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.<br /> [[Image:proteosome length.png| thumb |left | upright=0.75 |Length view of Proteasome]]<br /> [[Image:proteaosome top.png| thumb |right | upright=1.0 |Top view of proteasome]]<br /> <br /> =Types of Ubiquitin Conjugates=<br /> There are 3 different types of ubiquitin conjugates known:<br /> === Ubiquitinylation === <br /> <br /> =Diseases=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1062001 2010-03-29T01:03:53Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref&gt;Vijay-Kumar, S., Begg, CE. and Cook, WJ. 1987. Structure of Ubiquitin Refined at 1.8 Angstrom Resolution. J Mol Biol. 194: 531-544.&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> <br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> [[Image:Ubq_pathway.png| thumb |centre | upright=2.0 |Ubiquitinylation pathway]]<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref&gt;Cox, MJ., Haas, AL. and Wilkinson, KD. 1986. Role of ubiquitin conformations in the specificity of protein degradation: iodinated derivatives with altered conformations and activities. Arch Biochem Biophys. 250:00-409&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref&gt;Wilkinson, KD. 1997. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. FASEB J. 11:1245-1256&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be damaged, the ubiquitinylated protein is lead to its degradation by the 26S proteasome&lt;ref&gt;Hochstrasser, M. 1996. Ubiquitin-dependent protein Degradation. Annu Rev Genet. 30: 405-439&lt;/ref&gt;. The 26S proteasome is made up of a 20S core and a 19S cap. The targeted protein must be unfolded, deubiquitinylated and translocated through the 19S cap channels and into the proteasome interior. The 20S proteasome than cleaves the polypeptide into short peptides of roughly 7-9 fragment residues. This process is ATP-independent. Cytosolic peptidases then degrades the fragment into its appropriate amino acids. The ubiquitin molecules are returned to the cell where they are reused.<br /> [[Image:proteosome length.png| thumb |left | upright=0.75 |Length view of Proteasome]]<br /> [[Image:proteaosome top.png| thumb |right | upright=1.0 |Top view of proteasome]]<br /> <br /> =Types of Ubiquitin Conjugates=<br /> There are 3 different types of ubiquitin conjugates known:<br /> 1) Ubiquitinylation: <br /> =Diseases=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061991 2010-03-29T00:12:26Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref&gt;Vijay-Kumar, S., Begg, CE. and Cook, WJ. 1987. Structure of Ubiquitin Refined at 1.8 Angstrom Resolution. J Mol Biol. 194: 531-544.&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.[[image:1ubiq.png| thumb |none | upright=2.0 |Ubiquitin structure: Arg74 in pink and Gly75 Gly76 in white.]]<br /> <br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[image:lysubq.png| thumb |right | upright=2.0 |Ubiquitin structure with lysine residues highlighted in Yellow.]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> <br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png| thumb |none | upright=2.0 |Isopeptide bond between two Ubiquitin molecules]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> [[Image:Ubq_pathway.png| thumb |centre | upright=2.0 |Ubiquitinylation pathway]]<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref&gt;Cox, MJ., Haas, AL. and Wilkinson, KD. 1986. Role of ubiquitin conformations in the specificity of protein degradation: iodinated derivatives with altered conformations and activities. Arch Biochem Biophys. 250:00-409&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref&gt;Wilkinson, KD. 1997. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. FASEB J. 11:1245-1256&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be <br /> [[Image:proteosome length.png| thumb |left | upright=1.0 |Length view of Proteasome]]<br /> [[Image:proteaosome top.png| thumb |right | upright=1.0 |Top view of proteasome]]<br /> <br /> <br /> <br /> <br /> <br /> =Types of Ubiquitin Conjugates=<br /> =Diseases=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061980 2010-03-28T23:33:13Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref&gt;Vijay-Kumar, S., Begg, CE. and Cook, WJ. 1987. Structure of Ubiquitin Refined at 1.8 Angstrom Resolution. J Mol Biol. 194: 531-544.&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|350 px|center]]<br /> [[Image:1ubiq.png|350 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> <br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png|350 px|right]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref&gt;Cox, MJ., Haas, AL. and Wilkinson, KD. 1986. Role of ubiquitin conformations in the specificity of protein degradation: iodinated derivatives with altered conformations and activities. Arch Biochem Biophys. 250:00-409&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref&gt;Wilkinson, KD. 1997. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. FASEB J. 11:1245-1256&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be <br /> [[Image:proteosome length.png|200 px|center]]<br /> [[Image:proteaosome top.png|200 px|right]]<br /> <br /> =Types of Ubiquitin Conjugates=<br /> =Diseases=<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061795 2010-03-28T00:51:36Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref&gt;Vijay-Kumar, S., Begg, CE. and Cook, WJ. 1987. Structure of Ubiquitin Refined at 1.8 Angstrom Resolution. J Mol Biol. 194: 531-544.&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|350 px|center]]<br /> [[Image:1ubiq.png|350 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> <br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png|350 px|right]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref&gt;Cox, MJ., Haas, AL. and Wilkinson, KD. 1986. Role of ubiquitin conformations in the specificity of protein degradation: iodinated derivatives with altered conformations and activities. Arch Biochem Biophys. 250:00-409&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref&gt;Wilkinson, KD. 1997. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. FASEB J. 11:1245-1256&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be <br /> [[Image:proteosome length.png|200 px|center]]<br /> [[Image:proteaosome top.png|200 px|right]]<br /> <br /> == Types of Ubiquitin Conjugates ==<br /> == Diseases ==<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061787 2010-03-27T23:59:25Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref&gt;Vijay-Kumar, S., Begg, CE. and Cook, WJ. 1987. Structure of Ubiquitin Refined at 1.8 Angstrom Resolution. J Mol Biol. 194: 531-544.&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|350 px|center]]<br /> [[Image:1ubiq.png|350 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> <br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png|350 px|right]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref&gt;Cox, MJ., Haas, AL. and Wilkinson, KD. 1986. Role of ubiquitin conformations in the specificity of protein degradation: iodinated derivatives with altered conformations and activities. Arch Biochem Biophys. 250:00-409&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref&gt;Wilkinson, KD. 1997. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. FASEB J. 11:1245-1256&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be <br /> [[Image:proteosome length.png|200 px|center]][[Image:proteaosome top.png|200 px|right]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061786 2010-03-27T23:58:40Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref&gt;Vijay-Kumar, S., Begg, CE. and Cook, WJ. 1987. Structure of Ubiquitin Refined at 1.8 Angstrom Resolution. J Mol Biol. 194: 531-544.&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|350 px|center]]<br /> [[Image:1ubiq.png|350 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> <br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png|350 px|right]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref&gt;Cox, MJ., Haas, AL. and Wilkinson, KD. 1986. Role of ubiquitin conformations in the specificity of protein degradation: iodinated derivatives with altered conformations and activities. Arch Biochem Biophys. 250:00-409&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref&gt;Wilkinson, KD. 1997. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. FASEB J. 11:1245-1256&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be <br /> [[Image:proteosome length.png|100 px|center]][[Image:proteaosome top.png|350 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061785 2010-03-27T23:57:27Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref&gt;Vijay-Kumar, S., Begg, CE. and Cook, WJ. 1987. Structure of Ubiquitin Refined at 1.8 Angstrom Resolution. J Mol Biol. 194: 531-544.&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|350 px|center]]<br /> [[Image:1ubiq.png|350 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> [[Image:proteosome length.png|350 px|center]][[Image:proteosome top.png|350 px|center]]<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png|350 px|right]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref&gt;Cox, MJ., Haas, AL. and Wilkinson, KD. 1986. Role of ubiquitin conformations in the specificity of protein degradation: iodinated derivatives with altered conformations and activities. Arch Biochem Biophys. 250:00-409&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref&gt;Wilkinson, KD. 1997. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. FASEB J. 11:1245-1256&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be <br /> <br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=File:Proteosome_length.png&diff=1061783 2010-03-27T23:55:22Z

<p>Jaclyn Gordon: </p> <hr /> <div></div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061782 2010-03-27T23:53:21Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation&lt;ref&gt;Vijay-Kumar, S., Begg, CE. and Cook, WJ. 1987. Structure of Ubiquitin Refined at 1.8 Angstrom Resolution. J Mol Biol. 194: 531-544.&lt;/ref&gt;<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|350 px|center]]<br /> [[Image:1ubiq.png|350 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png|350 px|right]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref&gt;Cox, MJ., Haas, AL. and Wilkinson, KD. 1986. Role of ubiquitin conformations in the specificity of protein degradation: iodinated derivatives with altered conformations and activities. Arch Biochem Biophys. 250:00-409&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref&gt;Wilkinson, KD. 1997. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. FASEB J. 11:1245-1256&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be <br /> <br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061781 2010-03-27T23:51:26Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|350 px|center]]<br /> [[Image:1ubiq.png|350 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png|350 px|right]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref&gt;Cox, MJ., Haas, AL. and Wilkinson, KD. 1986. Role of ubiquitin conformations in the specificity of protein degradation: iodinated derivatives with altered conformations and activities. Arch Biochem Biophys. 250:00-409&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref&gt;Wilkinson, KD. 1997. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. FASEB J. 11:1245-1256&lt;/ref&gt;.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be <br /> <br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061780 2010-03-27T23:50:16Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|350 px|center]]<br /> [[Image:1ubiq.png|350 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png|350 px|right]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref&gt;Cox, MJ., Haas, AL. and Wilkinson, KD. 1986. Role of ubiquitin conformations in the specificity of protein degradation: iodinated derivatives with altered conformations and activities. Arch Biochem Biophys. 250:00-409&lt;/ref&gt;. This is done through the actions of deubiquitinating thiol proteases which recognize the native conformation of ubiquitin and cleave the isopeptide bond located at the carboxyl-terminal G76 of ubiquitin&lt;ref&gt;Wilkinson, KD. 1997. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes. FASEB J. 11:1245-1256.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be <br /> <br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061779 2010-03-27T23:38:10Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|350 px|center]]<br /> [[Image:1ubiq.png|350 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png|350 px|right]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> === Proofreading ===<br /> Before degradation is complete, the system must ensure that the protein that has been ubiquitinylated is in fact damaged. Enzymes associated with proofreading with either inhibit or stimulate ubiquitin-dependent processes. If the target protein is found to not be damaged, deconjugation of ubiquitin from mono- or polyubiquitinylated proteins will result in order to inhibit any further degradation processes. This reverse reaction is known as a &quot;futile cycle&quot;&lt;ref&gt;Cox, MJ., Haas, AL. and Wilkinson, KD. 1986. Role of ubiquitin conformations in the specificity of protein degradation: iodinated derivatives with altered conformations and activities. Arch Biochem Biophys. 250:00-409&lt;/ref&gt;. This is done through the actions of proteases which recognize the native conformation of ubiquitin.<br /> === Conjugate Metabolism ===<br /> If, however, the target protein is found to be <br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061772 2010-03-27T22:57:53Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|350 px|center]]<br /> [[Image:1ubiq.png|350 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png|350 px|right]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> === Proofreading ===<br /> <br /> === Conjugate Metabolism ===<br /> <br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061771 2010-03-27T22:56:22Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|350 px|center]]<br /> [[Image:1ubiq.png|350 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> The activated ubiquitin in then transferred to a ubiquitin-conjugating enzyme, E2 through a trans-thiolesteration reaction. Ubiquitin is then transferred to the ε-amino group of a lysine chain on the target protein. An isopeptide bond is now formed between the carboxyl terminal of ubiquitin and the ε-amino group of the target protein lysine residue. This is accomplished by E2 directly.<br /> [[Image:diubq.png|350 px|center]]<br /> Some proteins may be selected for degradation through the use of protein E3. E3 binds and catalyzes the isopeptide bond between ubiquitin and the target protein. Several activated ubiquitin may be added while still bound to E2 following the first ubiquitin addition.<br /> === Proofreading ===<br /> <br /> === Conjugate Metabolism ===<br /> <br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061671 2010-03-27T06:08:26Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|350 px|center]]<br /> [[Image:1ubiq.png|350 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> [[Image:diubq.png|350 px|center]]<br /> === Proofreading ===<br /> === Conjugate Metabolism ===<br /> <br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061670 2010-03-27T06:07:15Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|500 px|center]]<br /> [[Image:1ubiq.png|300 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of several seperate reactions:<br /> === Activation ===<br /> The first step of ubiquitin activation involves the formation of a ubiqiotin-adenylate intermediate. This reaction requires an E1 ubiquitin-activating enzyme. The second step of ubiquitin activation transfers ubiquitin to the E1 active site cysteine residue and AMP is released. This step results in a thioester linkage between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group.<br /> === Ubiquitin Conjugation ===<br /> === Proofreading ===<br /> === Conjugate Metabolism ===<br /> [[Image:diubq.png|500 px|center]]<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=File:Lysubq.png&diff=1061665 2010-03-27T05:55:48Z

<p>Jaclyn Gordon: </p> <hr /> <div></div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061664 2010-03-27T05:55:32Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:lysubq.png|500 px|center]]<br /> [[Image:1ubiq.png|300 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of 4 seperate reactions:<br /> === Activation ===<br /> <br /> [[Image:diubq.png|500 px|center]]<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061662 2010-03-27T05:53:05Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:1ubiq.png|300 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of 4 seperate reactions:<br /> === Activation ===<br /> <br /> [[Image:diubq.png|500 px|center]]<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=File:Diubq.png&diff=1061660 2010-03-27T05:52:27Z

<p>Jaclyn Gordon: </p> <hr /> <div></div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061659 2010-03-27T05:51:23Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:1ubiq.png|300 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of 4 seperate reactions:<br /> === Activation ===<br /> <br /> [[Image:Diubiquitin-lysine-48.png|500 px|center]]<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061658 2010-03-27T05:49:29Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:1ubiq.png|300 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of 4 seperate reactions:<br /> === Activation ===<br /> [[Imagine:Diubiquitin-lysine-48.png|400 px|right]]<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061627 2010-03-27T02:32:30Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:1ubiq.png|300 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today, ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of 4 seperate reactions:<br /> <br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061625 2010-03-27T02:27:53Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ubiquitin is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:1ubiq.png|300 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of 4 seperate reactions:<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061550 2010-03-26T22:00:10Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ub is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:1ubiq.png|300 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished through the process of 4 seperate reactions:<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061542 2010-03-26T21:26:09Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ub is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:1ubiq.png|300 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished by the formation of covalent conjugates between carboxyl terminals of ubiquitin and the target protein.<br /> [[Image:Ubq_pathway.png|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=File:Ubq_pathway.png&diff=1061541 2010-03-26T21:25:34Z

<p>Jaclyn Gordon: </p> <hr /> <div></div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061540 2010-03-26T21:22:55Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ub is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> [[Image:1ubiq.png|300 px|right]]<br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However, today ubiquitin is primarily known for its role in intracellular ATP-dependent protein degradation. This is accomplished by the formation of covalent conjugates between carboxyl terminals of ubiquitin and the target protein.<br /> [[Image:Ubiquitylation.svg|500 px|center]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061535 2010-03-26T21:12:06Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ub is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> <br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However,<br /> [[Image:1ubiq.png|300 px|right]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061534 2010-03-26T21:11:12Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ub is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> <br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However,<br /> [[Image:1ubiq.png|500 px|right]]<br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=File:1ubiq.png&diff=1061531 2010-03-26T21:09:51Z

<p>Jaclyn Gordon: </p> <hr /> <div></div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061524 2010-03-26T21:02:39Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ub is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> <br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However,<br /> <br /> &lt;references/&gt;</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061513 2010-03-26T20:54:34Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ub is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> <br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However,</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061509 2010-03-26T20:52:52Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ub is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> <br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However,<br /> [[Image:1ubq.png|500 px|right]]</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1061508 2010-03-26T20:52:10Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ub is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> <br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However,<br /> [[Image:schematic_NOS.png|500 px|right]]</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Inositol_1,4,5-Trisphosphate_Receptor&diff=1061428 2010-03-26T17:31:29Z

<p>Jaclyn Gordon: </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 /> <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>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1059158 2010-03-23T20:26:47Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ub is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> One interesting characteristic of ubiquitin is its stability. Ubiquitin is able to withstand a range of pH levels and temperatures and is very resistant to tryptic digestion, while still containing seven Lysine and four arginine residues. Many aspects of ubiquitin's structure aid in this durability. Ubiquitin contains a hydrophobic core. Three hydrophobic residues found on the α-helix and 11 of the 13 hydrophobic residues from the β-sheet are involved in constructing this hydrophobic core. The main contributor to the ubiquitin stability is the vast amount of hydrogen-bonding interactions observed. The whole structure of ubiquitin undergoes significant hydrogen bonding, aside from the COOH terminus. <br /> <br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;. However,</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1059105 2010-03-23T08:48:19Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ub is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> Put structure in with intro...<br /> <br /> =Function=<br /> At first, ubiquitin was believed to be a hormone involed in inducing the differentiation of lymphocytes and activating adenylate cyclase &lt;ref&gt;Vijay-Kumar, S., Begg, CE., Wilkinson, KD and Cook, WJ. 1985. Three-dimensional structure of ubiquitin of 2.8 angstrom resolution. ''Proc Natl Acad Sci'' 82:3582-3585&lt;/ref&gt;.</div>

Jaclyn Gordon https://proteopedia.org/index.php?title=Ubiquitin_Structure_%26_Function&diff=1059104 2010-03-23T08:41:22Z

<p>Jaclyn Gordon: </p> <hr /> <div>Ubiquitin is a single 8565 M&lt;sub&gt;r&lt;/sub&gt; polypeptide consisting of 76 amino acid residues. Ub is highly known for its role in ATP-dependant protein degradation.<br /> {{STRUCTURE_1ubq | PDB=1ubq | SCENE= }}<br /> <br /> =Introduction=<br /> Ubiquitin is one of the most highly conserved eukaryotic proteins. Primary structures found throughout ubiquitin are identical in all bovine, insects and human ubiquitin. The only difference observed amongst these species is seen in the terminal Gly-Gly residues. Yeast and oat ubiquitin only differ in three of the 76 residues when compared to ubiquitin found in higher eukaryotes.<br /> Ubiquitin can not only be found in the nucleus, but in the cytoplasm and cell-surface membrane as well.<br /> =Structure=<br /> =Function=</div>

Jaclyn Gordon