Proteopedia - User contributions [en]

Nuclear polyadenylated RNA-binding protein

2018-04-24T02:27:06Z

Matthew Douglas Moore:

<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>

=Introduction=
[[Image:Hrp1 fig1 cropped.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cerevisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) (Figure 1) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>. Hrp1 was discovered when Cleavage Factor I (CF I) was purified and separated into its two components, CF IA and CF IB. CF IB is a single 73 kDa polypeptide. The polypeptide was digested and two tryptic peptides were obtained for sequencing. The sequences were aligned via a database, and Hrp1 was determined to be a perfect match. Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage and polyadenylation of pre-mRNA and transport of mature mRNA from the nucleus<ref name="KHSZ">PMID: 9334319</ref>.

=Structure=
==General Features==
Hrp1 is a single-stranded [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. The kinked conformation around Ade4 is uncommon for RNA alone, and may be adopted by the RNA for specific interactions with Hrp1. Ade4 is part of a crucial interaction with Trp168 which will be discussed later, and could explain the adoption of the kinked conformation. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/783765/Ade4-trp168/4'>interaction between Ade4 and Trp168</scene> <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds such as the H-bond between N7 of Ade4 and amide hydrogren of Trp168 <ref name="GM3H"/>. This interaction is a unique feature of the Hrp1-PEE complex and has not been found in any other single-stranded RNA-binding proteins with two canonical RBDs <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/3'>Lys226</scene>, which stabilizes Ade4 likely via a [https://en.wikipedia.org/wiki/Cation%E2%80%93pi_interaction cation–π interaction]. As displayed in the structure, the lysine cationic nitrogen is approximately 4Å away from the pi system, which is within the 6Å range associated with cation-pi interactions. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/2'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix), which also contains a crucial residue for RNA binding. Ile234 in the linker region holds Ade6 in place in order to ensure proper <scene name='78/781945/Linker_rna/2'>via van der Waals contacts</scene> with the nearby Phe162. Experimental evidence from protein [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance nuclear magnetic resonance (NMR)] data <ref name="GM3H"/> suggests that the two RBDs move independently prior to binding the PEE. Upon binding the PEE, the linker region adopts a short helical structure to rigidly hold the RBDs in place relative to each other. Aside from the linker helix, the only other interaction between the RBDs is <scene name='78/781945/Interaction_between_domains/8'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.

[[Image:Hrp1 RNA15 Cropped.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (blue), RNA15 (orange) and RNA (green).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site (Figure 2) <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. These proteins, in addition to Hrp1 and Srp20, contain conserved hydrophobic residues which contribute to hydrophobic interactions between secondary structures of the proteins. Each protein also contains conserved residues L166 and G201 which form a hydrogen bond, linking the β-sheets in the βαβ complex of Hrp1 (Figure 3). [[Image:Conserved_Hrp1_sequence_logo.png|525 px|center|thumb|Figure 3: Sequence logo for residues 161-205 of Hrp1.]] Like Hrp1, each of these proteins belongs to the class of single-stranded proteins composed of two canonical RBDs; however, each protein is differentiated by respective target RNA sequences, interactions with RNA at the atomic level, and interdomain contacts <ref name="GM3H"/>. Hrp1 is unique in that HuD, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is lacking in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other protein-RNA complexes is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. This may help explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.
</StructureSection>

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-24T02:00:58Z

Matthew Douglas Moore:

<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>

=Introduction=
[[Image:Hrp1 fig1 cropped.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cerevisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) (Figure 1) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>. Hrp1 was discovered when Cleavage Factor I (CF I) was purified and separated into its two components, CF IA and CF IB. CF IB is a single 73 kDa polypeptide. The polypeptide was digested and two tryptic peptides were obtained for sequencing. The sequences were aligned via a database, and Hrp1 was determined to be a perfect match. Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage and polyadenylation of pre-mRNA and transport of mature mRNA from the nucleus<ref name="KHSZ">PMID: 9334319</ref>.

=Structure=
==General Features==
Hrp1 is a single-stranded [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. The kinked conformation around Ade4 is uncommon for RNA alone, and may be adopted by the RNA for specific interactions with Hrp1. Ade4 is part of a crucial interaction with Trp168 which will be discussed later, and could explain the adoption of the kinked conformation. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/783765/Ade4-trp168/4'>interaction between Ade4 and Trp168</scene> <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds such as the H-bond between N7 of Ade4 and amide hydrogren of Trp168 <ref name="GM3H"/>. This interaction is a unique feature of the Hrp1-PEE complex and has not been found in any other single-stranded RNA-binding proteins with two canonical RBDs <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/3'>Lys226</scene>, which stabilizes Ade4 likely via a [https://en.wikipedia.org/wiki/Cation%E2%80%93pi_interaction cation–π interaction]. As displayed in the structure, the lysine cationic nitrogen is approximately 4Å away from the pi system, which is within the 6Å range associated with cation-pi interactions. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/2'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix), which also contains a crucial residue for RNA binding. Ile234 in the linker region holds Ade6 in place in order to ensure proper <scene name='78/781945/Linker_rna/2'>via van der Waals contacts</scene> with the nearby Phe162. Experimental evidence from protein [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance nuclear magnetic resonance (NMR)] data <ref name="GM3H"/> suggests that the two RBDs move independently prior to binding the PEE. Upon binding the PEE, the linker region adopts a short helical structure to rigidly hold the RBDs in place relative to each other. Aside from the linker helix, the only other interaction between the RBDs is <scene name='78/781945/Interaction_between_domains/8'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.

[[Image:Hrp1 RNA15 Cropped.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (blue), RNA15 (orange) and RNA (green).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site (Figure 2) <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. These proteins, in addition to Hrp1 and Srp20, conserve specific hydrophobic residues which contribute to hydrophobic interactions between secondary structures of the proteins. Each of these proteins also conserves residues L166 and G201 which form a hydrogen bond, linking the β-sheets in the βαβ complex of Hrp1 (Figure 3). [[Image:Conserved_Hrp1_sequence_logo.png|525 px|center|thumb|Figure 3: Sequence logo for residues 161-205 of Hrp1.]] Like Hrp1, each of these proteins belong to the class of single-stranded proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.
</StructureSection>

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-24T01:59:58Z

Matthew Douglas Moore:

<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>

=Introduction=
[[Image:Hrp1 fig1 cropped.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cervisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) (Figure 1) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>. Hrp1 was discovered when Cleavage Factor I (CF I) was purified and separated into its two components, CF IA and CF IB. CF IB is a single 73 kDa polypeptide. The polypeptide was digested and two tryptic peptides were obtained for sequencing. The sequences were aligned via a database, and Hrp1 was determined to be a perfect match. Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage and polyadenylation of pre-mRNA and transport of mature mRNA from the nucleus<ref name="KHSZ">PMID: 9334319</ref>.

=Structure=
==General Features==
Hrp1 is a single-stranded [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. The kinked conformation around Ade4 is uncommon for RNA alone, and may be adopted by the RNA for specific interactions with Hrp1. Ade4 is part of a crucial interaction with Trp168 which will be discussed later, and could explain the adoption of the kinked conformation. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/783765/Ade4-trp168/4'>interaction between Ade4 and Trp168</scene> <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds such as the H-bond between N7 of Ade4 and amide hydrogren of Trp168 <ref name="GM3H"/>. This interaction is a unique feature of the Hrp1-PEE complex and has not been found in any other single-stranded RNA-binding proteins with two canonical RBDs <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/3'>Lys226</scene>, which stabilizes Ade4 likely via a [https://en.wikipedia.org/wiki/Cation%E2%80%93pi_interaction cation–π interaction]. As displayed in the structure, the lysine cationic nitrogen is approximately 4Å away from the pi system, which is within the 6Å range associated with cation-pi interactions. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/2'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix), which also contains a crucial residue for RNA binding. Ile234 in the linker region holds Ade6 in place in order to ensure proper <scene name='78/781945/Linker_rna/2'>via van der Waals contacts</scene> with the nearby Phe162. Experimental evidence from protein [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance nuclear magnetic resonance (NMR)] data <ref name="GM3H"/> suggests that the two RBDs move independently prior to binding the PEE. Upon binding the PEE, the linker region adopts a short helical structure to rigidly hold the RBDs in place relative to each other. Aside from the linker helix, the only other interaction between the RBDs is <scene name='78/781945/Interaction_between_domains/8'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.

[[Image:Hrp1 RNA15 Cropped.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (blue), RNA15 (orange) and RNA (green).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site (Figure 2) <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. These proteins, in addition to Hrp1 and Srp20, conserve specific hydrophobic residues which contribute to hydrophobic interactions between secondary structures of the proteins. Each of these proteins also conserves residues L166 and G201 which form a hydrogen bond, linking the β-sheets in the βαβ complex of Hrp1 (Figure 3). [[Image:Conserved_Hrp1_sequence_logo.png|525 px|center|thumb|Figure 3: Sequence logo for residues 161-205 of Hrp1.]] Like Hrp1, each of these proteins belong to the class of single-stranded proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.
</StructureSection>

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-24T01:54:36Z

Matthew Douglas Moore:

<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>

=Introduction=
[[Image:Hrp1 fig1 cropped.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cervisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) (Figure 1) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>. Hrp1 was discovered when Cleavage Factor I (CF I) was purified and separated into its two components, CF IA and CF IB. CF IB is a single 73 kDa polypeptide. The polypeptide was digested and two tryptic peptides were obtained for sequencing. The sequences were aligned via a database, and Hrp1 was determined to be a perfect match. Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage, polyadenylation, and mRNA transport from the nucleus<ref name="KHSZ">PMID: 9334319</ref>.

=Structure=
==General Features==
Hrp1 is a single-stranded [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. The kinked conformation around Ade4 is uncommon for RNA alone, and may be adopted by the RNA for specific interactions with Hrp1. Ade4 is part of a crucial interaction with Trp168 which will be discussed later, and could explain the adoption of the kinked conformation. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/783765/Ade4-trp168/4'>interaction between Ade4 and Trp168</scene> <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds such as the H-bond between N7 of Ade4 and amide hydrogren of Trp168 <ref name="GM3H"/>. This interaction is a unique feature of the Hrp1-PEE complex and has not been found in any other single-stranded RNA-binding proteins with two canonical RBDs <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/3'>Lys226</scene>, which stabilizes Ade4 likely via a [https://en.wikipedia.org/wiki/Cation%E2%80%93pi_interaction cation–π interaction]. As displayed in the structure, the lysine cationic nitrogen is approximately 4Å away from the pi system, which is within the 6Å range associated with cation-pi interactions. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/2'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix), which also contains a crucial residue for RNA binding. Ile234 in the linker region holds Ade6 in place in order to ensure proper <scene name='78/781945/Linker_rna/2'>via van der Waals contacts</scene> with the nearby Phe162. Experimental evidence from protein [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance nuclear magnetic resonance (NMR)] data <ref name="GM3H"/> suggests that the two RBDs move independently prior to binding the PEE. Upon binding the PEE, the linker region adopts a short helical structure to rigidly hold the RBDs in place relative to each other. Aside from the linker helix, the only other interaction between the RBDs is <scene name='78/781945/Interaction_between_domains/8'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.

[[Image:Hrp1 RNA15 Cropped.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (blue), RNA15 (orange) and RNA (green).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site (Figure 2) <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. These proteins, in addition to Hrp1 and Srp20, conserve specific hydrophobic residues which contribute to hydrophobic interactions between secondary structures of the proteins. Each of these proteins also conserves residues L166 and G201 which form a hydrogen bond, linking the β-sheets in the βαβ complex of Hrp1 (Figure 3). [[Image:Conserved_Hrp1_sequence_logo.png|525 px|center|thumb|Figure 3: Sequence logo for residues 161-205 of Hrp1.]] Like Hrp1, each of these proteins belong to the class of single-stranded proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.
</StructureSection>

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-24T01:30:15Z

Matthew Douglas Moore:

<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>

=Introduction=
[[Image:Hrp1 fig1 cropped.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cervisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) (Figure 1) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>. Hrp1 was discovered when Cleavage Factor I (CF I) was purified and separated into its two components, CF IA and CF IB. CF IB is a single 73 kDa polypeptide. The polypeptide was digested and two tryptic peptides were obtained for sequencing. The sequences were aligned via a database, and Hrp1 was determined to be a perfect match. Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage, polyadenylation, and mRNA transport from the nucleus<ref name="KHSZ">PMID: 9334319</ref>.

=Structure=
==General Features==
Hrp1 is a single-stranded [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. The kinked conformation around Ade4 is uncommon for RNA alone, and may be adopted by the RNA for specific interactions with Hrp1. Ade4 is part of a crucial interaction with Trp168 which will be discussed later, and could explain the adoption of the kinked conformation. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/783765/Ade4-trp168/4'>interaction between Ade4 and Trp168</scene> <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds such as the H-bond between N7 of Ade4 and amide hydrogren of Trp168 <ref name="GM3H"/>. This interaction is a unique feature of the Hrp1-PEE complex and has not been found in any other single-stranded RNA-binding proteins with two canonical RBDs <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/2'>Lys226</scene>, which stabilizes Ade4 likely via a [https://en.wikipedia.org/wiki/Cation%E2%80%93pi_interaction cation–π interaction]. As displayed in the structure, the lysine cationic nitrogen is approximately 4Å away from the pi system, which is within the 6Å range associated with cation-pi interactions. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/2'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix), which also contains a crucial residue for RNA binding. Ile234 in the linker region holds Ade6 in place in order to ensure proper <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene> with the nearby Phe162. Experimental evidence from protein [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance nuclear magnetic resonance (NMR)] data <ref name="GM3H"/> suggests that the two RBDs move independently prior to binding the PEE. Upon binding the PEE, the linker region adopts a short helical structure to rigidly hold the RBDs in place relative to each other. Aside from the linker helix, the only other interaction between the RBDs is <scene name='78/781945/Interaction_between_domains/8'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.

[[Image:Hrp1 RNA15 Cropped.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (blue), RNA15 (orange) and RNA (green).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site (Figure 2) <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. These proteins, in addition to Hrp1 and Srp20, conserve specific hydrophobic residues which contribute to hydrophobic interactions between secondary structures of the proteins. Each of these proteins also conserves residues L166 and G201 which form a hydrogen bond, linking the β-sheets in the βαβ complex of Hrp1 (Figure 3). [[Image:Conserved_Hrp1_sequence_logo.png|525 px|center|thumb|Figure 3: Sequence logo for residues 161-205 of Hrp1.]] Like Hrp1, each of these proteins belong to the class of single-stranded proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.
</StructureSection>

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-23T22:26:01Z

Matthew Douglas Moore:

<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>

=Introduction=
[[Image:Hrp1 fig1 cropped.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cervisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) (Figure 1) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>. Hrp1 was discovered when Cleavage Factor I (CF I) was purified and separated into its two components, CF IA and CF IB. CF IB is a single 73 kDa polypeptide. The polypeptide was digested and two tryptic peptides were obtained for sequencing. The sequences were aligned via a database, and Hrp1 was determined to be a perfect match. Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage, polyadenylation, and mRNA transport from the nucleus<ref name="KHSZ">PMID: 9334319</ref>.

=Structure=
==General Features==
Hrp1 is a single-stranded [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. The kinked conformation around Ade4 is uncommon for RNA alone, and may be adopted by the RNA for specific interactions with Hrp1. Ade4 is part of a crucial interaction with Trp168 which will be discussed later, and could explain the adoption of the kinked conformation. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/783765/Ade4-trp168/4'>interaction between Ade4 and Trp168</scene> <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds such as the H-bond between N7 of Ade4 and amide hydrogren of Trp168 <ref name="GM3H"/>. This interaction is a unique feature of the Hrp1-PEE complex and has not been found in any other single-stranded RNA-binding proteins with two canonical RBDs <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/2'>Lys226</scene>, which stabilizes Ade4 likely via a [https://en.wikipedia.org/wiki/Cation%E2%80%93pi_interaction cation–π interaction]. As displayed in the structure, the lysine cationic nitrogen is approximately 4Å away from the pi system, which is within the 6Å range associated with cation-pi interactions. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/1'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix), which also contains a crucial residue for RNA binding. Ile234 in the linker region holds Ade6 in place in order to ensure proper <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene> with the nearby Phe162. Experimental evidence from protein [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance nuclear magnetic resonance (NMR)] data <ref name="GM3H"/> suggests that the two RBDs move independently prior to binding the PEE. Upon binding the PEE, the linker region adopts a short helical structure to rigidly hold the RBDs in place relative to each other. Aside from the linker helix, the only other interaction between the RBDs is <scene name='78/781945/Interaction_between_domains/8'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.

[[Image:Hrp1 RNA15 Cropped.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (blue), RNA15 (orange) and RNA (green).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site (Figure 2) <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. These proteins, in addition to Hrp1 and Srp20, conserve specific hydrophobic residues which contribute to hydrophobic interactions between secondary structures of the proteins. Each of these proteins also conserves residues L166 and G201 which form a hydrogen bond, linking the β-sheets in the βαβ complex of Hrp1 (Figure 3). [[Image:Conserved_Hrp1_sequence_logo.png|525 px|center|thumb|Figure 3: Sequence logo for residues 161-205 of Hrp1.]] Like Hrp1, each of these proteins belong to the class of single-stranded proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.
</StructureSection>

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-23T22:03:33Z

Matthew Douglas Moore:

<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>

=Introduction=
[[Image:Hrp1 fig1 cropped.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cervisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) (Figure 1) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>. Hrp1 was discovered when Cleavage Factor I (CF I) was purified and separated into its two components, CF IA and CF IB. CF IB is a single 73 kDa polypeptide. The polypeptide was digested and two tryptic peptides were obtained for sequencing. The sequences were aligned via a database, and Hrp1 was determined to be a perfect match. Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage, polyadenylation, and mRNA transport from the nucleus<ref name="KHSZ">PMID: 9334319</ref>.

=Structure=
==General Features==
Hrp1 is a single-stranded [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. The kinked conformation around Ade4 is uncommon for RNA alone, and may be adopted by the RNA for specific interactions with Hrp1. Ade4 is part of a crucial interaction with Trp168 which will be discussed later, and could explain the adoption of the kinked conformation. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/783765/Ade4-trp168/4'>interaction between Ade4 and Trp168</scene> <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds such as the H-bond between N7 of Ade4 and amide hydrogren of Trp168 <ref name="GM3H"/>. This interaction is a unique feature of the Hrp1-PEE complex and has not been found in any other single-stranded RNA-binding proteins with two canonical RBDs <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/2'>Lys226</scene>, which stabilizes Ade4 likely via a [https://en.wikipedia.org/wiki/Cation%E2%80%93pi_interaction cation–π interaction]. As displayed in the structure, the lysine cationic nitrogen is approximately 4Å away from the pi system, which is within the 6Å range associated with cation-pi interactions. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/1'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix), which also contains a crucial residue for RNA binding. Ile234 in the linker region holds Ade6 in place in order to ensure proper <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene> with the nearby Phe162. Experimental evidence from protein [https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance nuclear magnetic resonance (NMR)] data <ref name="GM3H"/> suggests that the two RBDs move independently prior to binding the PEE. Upon binding the PEE, the linker region adopts a short helical structure to rigidly hold the RBDs in place relative to each other. Aside from the linker helix, the only other interaction between the RBDs is due to <scene name='78/781945/Interaction_between_domains/5'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.

[[Image:Hrp1 RNA15 Cropped.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (blue), RNA15 (orange) and RNA (green).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site (Figure 2) <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. These proteins, in addition to Hrp1 and Srp20, conserve specific hydrophobic residues which contribute to hydrophobic interactions between secondary structures of the proteins. Each of these proteins also conserves residues L166 and G201 which form a hydrogen bond, linking the β-sheets in the βαβ complex of Hrp1 (Figure 3.) [[Image:Conserved_Hrp1_sequence_logo.png|525 px|center|thumb|Figure 3: Sequence logo for residues 161-205 of Hrp1.]] Like Hrp1, each of these proteins belong to the class of single-stranded proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.
</StructureSection>

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-18T20:34:33Z

Matthew Douglas Moore:

<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>

=Introduction=
[[Image:Hrp1 fig1 cropped.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cervisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) (Figure 1) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>. Hrp1 was discovered when Cleavage Factor I (CF I) was purified and separated into its two components, CF IA and CF IB. CF IB is a single 73 kDa polypeptide. The polypeptide was digested and two tryptic peptides were obtained for sequencing. The sequences were aligned via a database, and Hrp1 was determined to be a perfect match. Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage, polyadenylation, and transport of the mRNA from the nucleus<ref name="KHSZ">PMID: 9334319</ref>.

=Structure=
==General Features==
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. The kinked conformation around Ade4 is uncommon for RNA alone, and may be adopted by the RNA for specific interactions with Hrp1. Ade4 is part of a crucial interaction with Trp168 which will be discussed later, and could explain the adoption of the kinked conformation. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue) <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/2'>Lys226</scene>, which stabilizes Ade4 likely via a [https://en.wikipedia.org/wiki/Cation%E2%80%93pi_interaction cation–π interaction]. As displayed in the structure, the lysine cationic nitrogen is approximately 4Å away from the pi system, which is within the 6Å range associated with cation-pi interactions. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/1'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix) which also contains an crucial residue for RNA binding. Ile234 holds Ade6 stacked in place with Phe162 <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene>. Experimental evidence from the NMR data <ref name="GM3H"/> suggests that the two RBDs at independently until binding the PEE. Binding the PEE causes the linker region to adopt a short helical structure to rigidly hold the <scene name='78/781945/Protein_domains/2'>RBDs in place relative to each other</scene>. Aside from the linker helix, the only interaction between the RBDs is due to <scene name='78/781945/Interaction_between_domains/5'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.

[[Image:Hrp1 RNA15 Cropped.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (blue), RNA15 (orange) and RNA (green).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

=Relationship to other proteins=
[[Image:Conserved W168 in Hrp1.png|250 px|right|thumb|Figure 3: Sequence logo for residues 167-169 of Hrp1. The logo displays the frequency of residues occuring at specific positions within Hrp1. W168 is always conserved in Hrp1 and RRMs of similar proteins.]]
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. Like Hrp1, each of these proteins belong to the class of single strand proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.
</StructureSection>

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-18T20:32:51Z

Matthew Douglas Moore:

<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>

=Introduction=
[[Image:Hrp1 fig1 cropped.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cervisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) (Figure 1) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>. Hrp1 was discovered when Cleavage Factor I (CF I) was purified and separated into its two components, CF IA and CF IB. CF IB is a single 73 kDa polypeptide. The polypeptide was digested and two tryptic peptides were obtained for sequencing. The sequences were aligned via a database, and Hrp1 was determined to be a perfect match. Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage, polyadenylation, and transport of the mRNA from the nucleus<ref name="KHSZ">PMID: 9334319</ref>.

=Structure=
==General Features==
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. The kinked conformation around Ade4 is uncommon for RNA alone, and may be adopted by the RNA for specific interactions with Hrp1. Ade4 is part of a crucial interaction with Trp168 which will be discussed later, and could explain the adoption of the kinked conformation. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue) <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/2'>Lys226</scene>, which stabilizes Ade4 likely via a [https://en.wikipedia.org/wiki/Cation%E2%80%93pi_interaction cation–π interaction]. As displayed in the structure, the lysine cationic nitrogen is about 4Å away from the pi system, within the 6Å range associated with cation-pi interactions. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/1'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix) which also contains an crucial residue for RNA binding. Ile234 holds Ade6 stacked in place with Phe162 <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene>. Experimental evidence from the NMR data <ref name="GM3H"/> suggests that the two RBDs at independently until binding the PEE. Binding the PEE causes the linker region to adopt a short helical structure to rigidly hold the <scene name='78/781945/Protein_domains/2'>RBDs in place relative to each other</scene>. Aside from the linker helix, the only interaction between the RBDs is due to <scene name='78/781945/Interaction_between_domains/5'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.

[[Image:Hrp1 RNA15 Cropped.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (blue), RNA15 (orange) and RNA (green).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

=Relationship to other proteins=
[[Image:Conserved W168 in Hrp1.png|250 px|right|thumb|Figure 3: Sequence logo for residues 167-169 of Hrp1. The logo displays the frequency of residues occuring at specific positions within Hrp1. W168 is always conserved in Hrp1 and RRMs of similar proteins.]]
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. Like Hrp1, each of these proteins belong to the class of single strand proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.
</StructureSection>

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-17T15:57:35Z

Matthew Douglas Moore:

<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>

=Introduction=
[[Image:Hrp1 fig1 cropped.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cervisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) (Figure 1) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>. Hrp1 was discovered when Cleavage Factor I (CF I) was purified and separated into its two components, CF IA and CF IB. CF IB is a single 73 kDa polypeptide. The polypeptide was digested and two tryptic peptides were obtained for sequencing. The sequences were aligned via a database, and Hrp1 was determined to be a perfect match. Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage, polyadenylation, and transport of the mRNA from the nucleus<ref name="KHSZ">PMID: 9334319</ref>.

=Structure=
==General Features==
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. The kinked conformation around Ade4 is uncommon for RNA alone, and may be adopted by the RNA for specific interactions with Hrp1. Ade4 is part of a crucial interaction with Trp168 which will be discussed later, and could explain the adoption of the kinked conformation. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue) <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/1'>Lys226</scene>, which stabilizes Ade4 via [https://en.wikipedia.org/wiki/Cation%E2%80%93pi_interaction] a cation pi interaction<ref name="GM3H"/>. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/1'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix) which also contains an crucial residue for RNA binding. Ile234 holds Ade6 stacked in place with Phe162 <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene>. Experimental evidence from the NMR data <ref name="GM3H"/> suggests that the two RBDs at independently until binding the PEE. Binding the PEE causes the linker region to adopt a short helical structure to rigidly hold the <scene name='78/781945/Protein_domains/2'>RBDs in place relative to each other</scene>. Aside from the linker helix, the only interaction between the RBDs is due to <scene name='78/781945/Interaction_between_domains/5'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.

[[Image:Hrp1 RNA15 Cropped.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (blue), RNA15 (orange) and RNA (green).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

=Relationship to other proteins=
[[Image:Conserved W168 in Hrp1.png|250 px|right|thumb|Figure 3: Sequence logo for residues 167-169 of Hrp1. The logo displays the frequency of residues occuring at specific positions within Hrp1. W168 is always conserved in Hrp1 and RRMs of similar proteins.]]
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. Like Hrp1, each of these proteins belong to the class of single strand proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.
</StructureSection>

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-17T15:55:04Z

Matthew Douglas Moore:

<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>

=Introduction=
[[Image:Hrp1 fig1 cropped.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cervisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) (Figure 1) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>. Hrp1 was discovered when Cleavage Factor I (CF I) was purified and separated into its two components, CF IA and CF IB. CF IB is a single 73 kDa polypeptide. The polypeptide was digested and two tryptic peptides were obtained for sequencing. The sequences were aligned via a database, and Hrp1 was determined to be a perfect match. Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage, polyadenylation, and transport of the mRNA from the nucleus<ref name="KHSZ">PMID: 9334319</ref>.

=Structure=
==General Features==
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. The kinked conformation around Ade4 is uncommon for RNA alone, and may be adopted by the RNA for specific interactions with Hrp1. Ade4 is part of a crucial interaction with Trp168 which will be discussed later, and could explain the adoption of the kinked conformation. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue) <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/1'>Lys226</scene>, which stabilizes Ade4 via [https://en.wikipedia.org/wiki/Cation%E2%80%93pi_interaction]<ref name="GM3H"/>. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/1'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix) which also contains an crucial residue for RNA binding. Ile234 holds Ade6 stacked in place with Phe162 <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene>. Experimental evidence from the NMR data <ref name="GM3H"/> suggests that the two RBDs at independently until binding the PEE. Binding the PEE causes the linker region to adopt a short helical structure to rigidly hold the <scene name='78/781945/Protein_domains/2'>RBDs in place relative to each other</scene>. Aside from the linker helix, the only interaction between the RBDs is due to <scene name='78/781945/Interaction_between_domains/5'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.

[[Image:Hrp1 RNA15 Cropped.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (blue), RNA15 (orange) and RNA (green).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

[[Image:Conserved W168 in Hrp1.png|250 px|right|thumb|Figure 3: Sequence logo for residues 167-169 of Hrp1. The logo displays the frequency of residues occuring at specific positions within Hrp1. W168 is always conserved in Hrp1 and RRMs of similar proteins.]]

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. Like Hrp1, each of these proteins belong to the class of single strand proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.
</StructureSection>

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-17T15:20:06Z

Matthew Douglas Moore:

=Introduction=
[[Image:Hrp1 cropped1.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cervisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. It was discovered when Cleavage Factor I (CF I) was purified and separated into its two components, CF IA and CF IB. CF IB is a single 73 kDa polypeptide. The polypeptide was digested and two tryptic peptides were obtained for sequencing. The sequences were aligned via a database, and Hrp1 was determined to be a perfect match. Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage, polyadenylation, and transport of the mRNA from the nucleus<ref name="KHSZ">PMID: 9334319</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>.

=Structure=
<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>
==General Features==
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. The kinked conformation around Ade4 is uncommon for RNA alone, and may be adopted by the RNA for specific interactions with Hrp1. Ade4 is part of a crucial interaction with Trp168 which will be discussed later, and could explain the adoption of the kinked conformation. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue) <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/1'>Lys226</scene>, which interacts via hydrogen bond with the N1 of Ade4 <ref name="GM3H"/>. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/1'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix) which also contains an crucial residue for RNA binding. Ile234 holds Ade6 stacked in place with Phe162 <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene>. Experimental evidence from the NMR data <ref name="GM3H"/> suggests that the two RBDs at independently until binding the PEE. Binding the PEE causes the linker region to adopt a short helical structure to rigidly hold the <scene name='78/781945/Protein_domains/2'>RBDs in place relative to each other</scene>. Aside from the linker helix, the only interaction between the RBDs is due to <scene name='78/781945/Interaction_between_domains/5'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.
</StructureSection>

[[Image:Hrp1 RNA15 Cropped.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (blue), RNA15 (orange) and RNA (green).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

[[Image:Conserved W168 in Hrp1.png|300 px|right|thumb|Figure 3: Sequence logo for residues 167-169 of Hrp1. The logo displays the frequency of residues occuring at specific positions within Hrp1. W168 is always conserved in Hrp1 and RRMs of similar proteins.]]

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. Like Hrp1, each of these proteins belong to the class of single strand proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-08T18:50:32Z

Matthew Douglas Moore:

=Introduction=
[[Image:Hrp1 cropped1.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in ''Saccharomyces cervisiae'' (yeast) <ref name="GM3H">PMID: 16794580</ref>. It has been determined to be the B subunit of Cleavage Factor I (CF I). Hrp1 of CF IB interacts with Rna14 and Rna15 of CF IA<ref name="RNA15"/> to form a protein complex that aids in cleavage, polyadenylation, and transport of the mRNA from the nucleus<ref name="KHSZ">PMID: 9334319</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>.

=Structure=
<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>
==General Features==
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue) <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/1'>Lys226</scene>, which interacts via hydrogen bond with the N1 of Ade4 <ref name="GM3H"/>. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/1'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix) which also contains an crucial residue for RNA binding. Ile234 holds Ade6 stacked in place with Phe162 <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene>. Experimental evidence from the NMR data <ref name="GM3H"/> suggests that the two RBDs at independently until binding the PEE. Binding the PEE causes the linker region to adopt a short helical structure to rigidly hold the <scene name='78/781945/Protein_domains/2'>RBDs in place relative to each other</scene>. Aside from the linker helix, the only interaction between the RBDs is due to <scene name='78/781945/Interaction_between_domains/5'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.
</StructureSection>

[[Image:Hrp1-RNA15.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (red), RNA15 (green) and RNA (blue).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

[[Image:Conserved W168 in Hrp1.png|300 px|right|thumb|Figure 3: Sequence logo for residues 167-169 of Hrp1. The logo displays the frequency of residues occuring at specific positions within Hrp1. W168 is always conserved in Hrp1 and RRMs of similar proteins.]]

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. Like Hrp1, each of these proteins belong to the class of single strand proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.

=References=
<references/>

User:Matthew Douglas Moore

2018-04-08T17:06:03Z

Matthew Douglas Moore:

* Full Real Name: Matthew D. Moore

* Position: Undergraduate Student

* Institution (NO ABBREVIATIONS): Butler University

* City, State/Province, Country: Indianapolis, Indiana, United States of America

* Field of Expertise or Study: Chemistry

[[User:Matthew Douglas Moore/Sandbox 1]]

Nuclear polyadenylated RNA-binding protein

2018-04-03T16:07:04Z

Matthew Douglas Moore:

=Introduction=
[[Image:Hrp1 cropped1.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in Saccharomyces cervisiae (yeast) <ref name="GM3H">PMID: 16794580</ref>. It is part of the Cleavage Factor I (CF I) B component. Hrp1 of CFIB interacts with Rna14 and Rna15 of CF IA <ref name="RNA15"/>. These complexes aid in cleavage, polyadenylation, and transport of the mRNA from the nucleus <ref name="KHSZ">PMID: 9334319</ref>. Hrp1 specifically recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>.

=Structure=
<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>
==General Features==
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue) <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/1'>Lys226</scene>, which interacts via hydrogen bond with the N1 of Ade4 <ref name="GM3H"/>. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/1'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix) which also contains an crucial residue for RNA binding. Ile234 holds Ade6 stacked in place with Phe162 <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene>. Experimental evidence from the NMR data <ref name="GM3H"/> suggests that the two RBDs at independently until binding the PEE. Binding the PEE causes the linker region to adopt a short helical structure to rigidly hold the <scene name='78/781945/Protein_domains/2'>RBDs in place relative to each other</scene>. Aside from the linker helix, the only interaction between the RBDs is due to <scene name='78/781945/Interaction_between_domains/5'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.
</StructureSection>

[[Image:Hrp1-RNA15.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (red), RNA15 (green) and RNA (blue).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

[[Image:Conserved W168 in Hrp1.png|300 px|right|thumb|Figure 3: Sequence logo for residues 167-169 of Hrp1. The logo displays the frequency of residues occuring at specific positions within Hrp1. W168 is always conserved in Hrp1 and RRMs of similar proteins.]]

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. Like Hrp1, each of these proteins belong to the class of single strand proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-03T15:59:31Z

Matthew Douglas Moore:

=Introduction=
[[Image:Hrp1 cropped1.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in Saccharomyces cervisiae (yeast) <ref name="GM3H">PMID: 16794580</ref>. It is part of the Cleavage Factor I (CFI) B component. As mentioned below, Hrp1 of CFIB interacts with Rna14 and Rna15 of CFIA. These complexes aid in cleavage, polyadenylation, and transport of the mRNA from the nucleus <ref name="KHSZ">PMID: 9334319</ref>. This protein recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>.

=Structure=
<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>
==General Features==
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue) <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/1'>Lys226</scene>, which interacts via hydrogen bond with the N1 of Ade4 <ref name="GM3H"/>. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/1'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix) which also contains an crucial residue for RNA binding. Ile234 holds Ade6 stacked in place with Phe162 <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene>. Experimental evidence from the NMR data <ref name="GM3H"/> suggests that the two RBDs at independently until binding the PEE. Binding the PEE causes the linker region to adopt a short helical structure to rigidly hold the <scene name='78/781945/Protein_domains/2'>RBDs in place relative to each other</scene>. Aside from the linker helix, the only interaction between the RBDs is due to <scene name='78/781945/Interaction_between_domains/5'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.
</StructureSection>

[[Image:Hrp1-RNA15.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (red), RNA15 (green) and RNA (blue).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

[[Image:Conserved W168 in Hrp1.png|300 px|right|thumb|Figure 3: Sequence logo for residues 167-169 of Hrp1. The logo displays the frequency of residues occuring at specific positions within Hrp1. W168 is always conserved in Hrp1 and RRMs of similar proteins.]]

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. Like Hrp1, each of these proteins belong to the class of single strand proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.

=References=
<references/>

Nuclear polyadenylated RNA-binding protein

2018-04-03T15:52:32Z

Matthew Douglas Moore:

=Introduction=
[[Image:Hrp1 cropped1.png|250 px|right|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element.]]
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in Saccharomyces cervisiae (yeast) <ref name="GM3H">PMID: 16794580</ref>. It is part of the Cleavage Factor I (CFI) B component. As mentioned below, Hrp1 of CFIB interacts with Rna14 and Rna15 of CFIA. These complexes aid in cleavage, polyadenylation, and transport of the mRNA from the nucleus. This protein recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] of the [https://en.wikipedia.org/wiki/Messenger_RNA messenger RNA (mRNA)] upstream from the cleavage site called the polyadenylation enhancement element (PEE) <ref name="GM3H"/>. Upon binding to the RNA, Hrp1 helps recruit additional proteins necessary for the cleavage and polyadenylation of the RNA molecule <ref name="GM3H"/>. Although Hrp1 shares several common features with other RNA-binding proteins, the unique structural features of the Hrp1-PEE complex reveals the mechanism by which Hrp1 is able to recognize and bind to its specific RNA sequence at the atomic level <ref name="GM3H"/>.

=Structure=
<StructureSection load='2cjk' size='400' side='right' caption='Hrp1-PEE Complex' scene='78/781945/Hrp1_and_pee/1'>
==General Features==
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central [https://en.wikipedia.org/wiki/Beta_sheet antiparallel] four-stranded <scene name='78/783765/Beta_sheet/1'>ß-sheet</scene> with two [https://en.wikipedia.org/wiki/Alpha_helix α-helices] running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.

==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA nucleobases <ref name="GM3H"/>. Only six RNA bases, an <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> repeat, act as the PEE and form specific contacts with Hrp1 <ref name="GM3H"/>. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding <ref name="GM3H"/>. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition <ref name="GM3H"/>. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue) <ref name="GM3H"/>. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds <ref name="GM3H"/>. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/1'>Lys226</scene>, which interacts via hydrogen bond with the N1 of Ade4 <ref name="GM3H"/>. A third contributor, <scene name='78/783765/Phe204_and_u7_interaction/1'>Phe204</scene>, also stacks with Ura7 to aid in RNA recognition and binding <ref name="GM3H"/>.

==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a <scene name='78/783765/Linker/3'>linker region</scene> (a short two-turn α-helix) which also contains an crucial residue for RNA binding. Ile234 holds Ade6 stacked in place with Phe162 <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene>. Experimental evidence from the NMR data <ref name="GM3H"/> suggests that the two RBDs at independently until binding the PEE. Binding the PEE causes the linker region to adopt a short helical structure to rigidly hold the <scene name='78/781945/Protein_domains/2'>RBDs in place relative to each other</scene>. Aside from the linker helix, the only interaction between the RBDs is due to <scene name='78/781945/Interaction_between_domains/5'>a single salt bridge</scene> between Lys231 and Asp271 <ref name="GM3H"/>.
</StructureSection>

[[Image:Hrp1-RNA15.png|200 px|left|thumb|Figure 2: Interaction between Hrp1 (red), RNA15 (green) and RNA (blue).]]

=Interaction with RNA15=
RNA15 is another RNA-binding protein with a single N-terminal RNA recognition motif (RRM) <ref name="RNA15">PMID: 20600122</ref>. RNA15 recognizes an A-rich positioning element (PE) downstream from the PEE but upstream from the 3' cleavage site <ref name="RNA15"/>. The recognition of the PE by RNA15 is crucial for precise cleavage of the RNA molecule. Hrp1 and RNA15 are held together by a separate protein, RNA14 <ref name="RNA15"/>. These proteins act together to anchor the polyadenylation and cleavage protein machinery relative to the cleavage site for precise 3'-end processing <ref name="RNA15"/>.

[[Image:Conserved W168 in Hrp1.png|300 px|right|thumb|Figure 3: Sequence logo for residues 167-169 of Hrp1. The logo displays the frequency of residues occuring at specific positions within Hrp1. W168 is always conserved in Hrp1 and RRMs of similar proteins.]]

=Relationship to other proteins=
The RNP-type RBD is found in many proteins involved in post-transcriptional [https://en.wikipedia.org/wiki/Post-transcriptional_modification pre-mRNA processing] (5'-end capping, splicing, 3'-end cleavage and polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>. The unique RBD of Hrp1 enables the protein to bind an RNA sequence that differs in both length and content from the RNA sequences of other RNA-binding and mRNA processing proteins such as [http://proteopedia.org/wiki/index.php/2sxl sex lethal], [https://en.wikipedia.org/wiki/Poly(A)-binding_protein Poly (A)-binding protein (PABP)], and [http://proteopedia.org/wiki/index.php/1fxl HuD] <ref name="GM3H"/>. Like Hrp1, each of these proteins belong to the class of single strand proteins composed of two canonical RBDs; however, these proteins are differentiated by their target RNA sequence, their interactions with RNA at the atomic level, and their interdomain contacts <ref name="GM3H"/>. One way in which Hrp1 differentiates itself from these other proteins is by the fact that Hud, sex lethal, and PABP all contain at least one intra-RNA base-base stacking interaction, a feature that is not found in the Hrp1-PEE complex <ref name="GM3H"/>. It is possible that the intra-RNA interactions found in these other proteins is replaced by the crucial Trp168-Ade4 stacking interaction found in the Hrp1 complex <ref name="GM3H"/>. The fact that the intra-RNA base-base stacking interactions are replaced by the Trp168-Ade4 in the Hrp1-PEE complex might also explain why the Hrp1-RNA interface involves only 6 nucleotides whereas PABP, sex lethal, and HuD require a longer 8-10 nucleotide sequence in the RNA binding pocket <ref name="GM3H"/>.

=References=
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-28T01:30:05Z

Matthew Douglas Moore:

=Introduction=
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='78/781945/Hrp1_and_pee/1' />
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in Saccharomyces cervisiae (yeast) <ref name="GM3H">PMID: 16794580</ref>. This protein recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] called the polyadenylation enhancement element (PEE) <ref name="GM3H"/>.

=Structure=
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central antiparallel four-stranded <scene name='78/781960/Beta_sheet/1'>ß-sheet</scene> with two α-helices running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.
[[Image:Hrp1 structure cropped for protopedia.png|350 px|left|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element. Notice the interface between the ß-sheets of Hrp1 and the RNA.]]
==Hrp1-RNA Interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA bases. Only six RNA bases, an (AU)3 repeat, act as the PEE and form specific contacts with Hrp1. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue). In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, <scene name='78/781945/Lys226-ade4-trp168/1'>Lys226</scene>, which interacts via hydrogen bond with the N1 of Ade4.
==RBD-RBD Interactions and the Linker Region==
As mentioned above, Hrp1 is composed of two RBDs. The RBDs are connected by a linker region which also contains an crucial residue for RNA binding. Ile234 holds Ade6 stacked in place with Phe162 <scene name='78/781945/Linker_rna/1'>via van der Waals contacts</scene>. Experimental evidence from the NMR data <ref name="GM3H"/> suggests that the two RBDs act independently until binding the PEE. Binding the PEE causes the linker region to adopt a short helical structure to rigidly hold the <scene name='78/781945/Protein_domains/2'>RBDs in place relative to each other</scene>. Aside from the linker helix, the only interaction between the RBDs is due to <scene name='78/781945/Interaction_between_domains/5'>a single salt bridge</scene> between Lys231 and Asp271.

=Relevance=

==Relationships to other proteins==
The RNP-type RBD is found in many proteins involved in post-transcriptional pre-mRNA processing (5' end capping, splicing, 3' end polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>.

==Interaction with RNA15==

=References=
<references/>
1. Pérez-Cañadillas, J. Grabbing The Message: Structural Basis Of Mrna 3′UTR Recognition By Hrp1. The EMBO Journal 2006, 25, 3167-3178.
2. Cléry, A.; Blatter, M.; Allain, F. RNA Recognition Motifs: Boring? Not Quite. Current Opinion in Structural Biology 2008, 18, 290-298.
3. Guo, Z.; Sherman, F. 3′-End-Forming Signals Of Yeast Mrna. Trends in Biochemical Sciences 1996, 21, 477-481.
4. Kessler, M.; Henry, M.; Shen, E.; Zhao, J.; Gross, S.; Silver, P.; Moore, C. Hrp1, A Sequence-Specific RNA-Binding Protein That Shuttles Between The Nucleus And The Cytoplasm, Is Required For Mrna 3'-End Formation In Yeast. Genes & Development 1997, 11, 2545-2556.
5. Leeper, T.; Qu, X.; Lu, C.; Moore, C.; Varani, G. Novel Protein–Protein Contacts Facilitate Mrna 3′-Processing Signal Recognition By Rna15 And Hrp1. Journal of Molecular Biology 2010, 401, 334-349.
6. The PyMol Molecular Graphics System, Version 2.0 Schrödinger, LLC. (for structural depictions)

User:Matthew Douglas Moore/Sandbox 1

2018-03-27T23:40:27Z

Matthew Douglas Moore:

=Introduction=
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='78/781945/Hrp1_and_pee/1' />
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in Saccharomyces cervisiae (yeast) <ref name="GM3H">PMID: 16794580</ref>. This protein recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] called the polyadenylation enhancement element (PEE) <ref name="GM3H"/>.

=Structure=
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central antiparallel four-stranded <scene name='78/781960/Beta_sheet/1'>ß-sheet</scene> with two α-helices running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.
[[Image:Hrp1 structure cropped for protopedia.png|350 px|left|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element. Notice the interface between the ß-sheets of Hrp1 and the RNA.]]
==Hrp1-RNA interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA bases. Only six RNA bases, an (AU)3 repeat, act as the PEE and form specific contacts with Hrp1. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue). In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds.

=Relevance=

==Relationships to other proteins==
The RNP-type RBD is found in many proteins involved in post-transcriptional pre-mRNA processing (5' end capping, splicing, 3' end polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>.

==Interaction with RNA15==

=References=
<references/>
1. Pérez-Cañadillas, J. Grabbing The Message: Structural Basis Of Mrna 3′UTR Recognition By Hrp1. The EMBO Journal 2006, 25, 3167-3178.
2. Cléry, A.; Blatter, M.; Allain, F. RNA Recognition Motifs: Boring? Not Quite. Current Opinion in Structural Biology 2008, 18, 290-298.
3. Guo, Z.; Sherman, F. 3′-End-Forming Signals Of Yeast Mrna. Trends in Biochemical Sciences 1996, 21, 477-481.
4. Kessler, M.; Henry, M.; Shen, E.; Zhao, J.; Gross, S.; Silver, P.; Moore, C. Hrp1, A Sequence-Specific RNA-Binding Protein That Shuttles Between The Nucleus And The Cytoplasm, Is Required For Mrna 3'-End Formation In Yeast. Genes & Development 1997, 11, 2545-2556.
5. Leeper, T.; Qu, X.; Lu, C.; Moore, C.; Varani, G. Novel Protein–Protein Contacts Facilitate Mrna 3′-Processing Signal Recognition By Rna15 And Hrp1. Journal of Molecular Biology 2010, 401, 334-349.
6. The PyMol Molecular Graphics System, Version 2.0 Schrödinger, LLC. (for structural depictions)

User:Matthew Douglas Moore/Sandbox 1

2018-03-27T23:29:24Z

Matthew Douglas Moore:

=Introduction=
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='78/781945/1'>
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in Saccharomyces cervisiae (yeast) <ref name="GM3H">PMID: 16794580</ref>. This protein recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] called the polyadenylation enhancement element (PEE) <ref name="GM3H"/>.

=Structure=
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central antiparallel four-stranded <scene name='78/781960/Beta_sheet/1'>ß-sheet</scene> with two α-helices running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.
[[Image:Hrp1 structure cropped for protopedia.png|350 px|left|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element. Notice the interface between the ß-sheets of Hrp1 and the RNA.]]
==Hrp1-RNA interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA bases. Only six RNA bases, an (AU)3 repeat, act as the PEE and form specific contacts with Hrp1. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue). In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds.

=Relevance=

==Relationships to other proteins==
The RNP-type RBD is found in many proteins involved in post-transcriptional pre-mRNA processing (5' end capping, splicing, 3' end polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>.

==Interaction with RNA15==

=References=
<references/>
1. Pérez-Cañadillas, J. Grabbing The Message: Structural Basis Of Mrna 3′UTR Recognition By Hrp1. The EMBO Journal 2006, 25, 3167-3178.
2. Cléry, A.; Blatter, M.; Allain, F. RNA Recognition Motifs: Boring? Not Quite. Current Opinion in Structural Biology 2008, 18, 290-298.
3. Guo, Z.; Sherman, F. 3′-End-Forming Signals Of Yeast Mrna. Trends in Biochemical Sciences 1996, 21, 477-481.
4. Kessler, M.; Henry, M.; Shen, E.; Zhao, J.; Gross, S.; Silver, P.; Moore, C. Hrp1, A Sequence-Specific RNA-Binding Protein That Shuttles Between The Nucleus And The Cytoplasm, Is Required For Mrna 3'-End Formation In Yeast. Genes & Development 1997, 11, 2545-2556.
5. Leeper, T.; Qu, X.; Lu, C.; Moore, C.; Varani, G. Novel Protein–Protein Contacts Facilitate Mrna 3′-Processing Signal Recognition By Rna15 And Hrp1. Journal of Molecular Biology 2010, 401, 334-349.
6. The PyMol Molecular Graphics System, Version 2.0 Schrödinger, LLC. (for structural depictions)

User:Matthew Douglas Moore/Sandbox 1

2018-03-27T23:28:42Z

Matthew Douglas Moore:

=Introduction=
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='78/781945/Hrp1_and_pee/1'>
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in Saccharomyces cervisiae (yeast) <ref name="GM3H">PMID: 16794580</ref>. This protein recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] called the polyadenylation enhancement element (PEE) <ref name="GM3H"/>.

=Structure=
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central antiparallel four-stranded <scene name='78/781960/Beta_sheet/1'>ß-sheet</scene> with two α-helices running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.
[[Image:Hrp1 structure cropped for protopedia.png|350 px|left|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element. Notice the interface between the ß-sheets of Hrp1 and the RNA.]]
==Hrp1-RNA interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA bases. Only six RNA bases, an (AU)3 repeat, act as the PEE and form specific contacts with Hrp1. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue). In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds.

=Relevance=

==Relationships to other proteins==
The RNP-type RBD is found in many proteins involved in post-transcriptional pre-mRNA processing (5' end capping, splicing, 3' end polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>.

==Interaction with RNA15==

=References=
<references/>
1. Pérez-Cañadillas, J. Grabbing The Message: Structural Basis Of Mrna 3′UTR Recognition By Hrp1. The EMBO Journal 2006, 25, 3167-3178.
2. Cléry, A.; Blatter, M.; Allain, F. RNA Recognition Motifs: Boring? Not Quite. Current Opinion in Structural Biology 2008, 18, 290-298.
3. Guo, Z.; Sherman, F. 3′-End-Forming Signals Of Yeast Mrna. Trends in Biochemical Sciences 1996, 21, 477-481.
4. Kessler, M.; Henry, M.; Shen, E.; Zhao, J.; Gross, S.; Silver, P.; Moore, C. Hrp1, A Sequence-Specific RNA-Binding Protein That Shuttles Between The Nucleus And The Cytoplasm, Is Required For Mrna 3'-End Formation In Yeast. Genes & Development 1997, 11, 2545-2556.
5. Leeper, T.; Qu, X.; Lu, C.; Moore, C.; Varani, G. Novel Protein–Protein Contacts Facilitate Mrna 3′-Processing Signal Recognition By Rna15 And Hrp1. Journal of Molecular Biology 2010, 401, 334-349.
6. The PyMol Molecular Graphics System, Version 2.0 Schrödinger, LLC. (for structural depictions)

User:Matthew Douglas Moore/Sandbox 1

2018-03-27T23:27:45Z

Matthew Douglas Moore:

=Introduction=
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='78/781945/Hrp1_and_pee/1'>' />
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in Saccharomyces cervisiae (yeast) <ref name="GM3H">PMID: 16794580</ref>. This protein recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] called the polyadenylation enhancement element (PEE) <ref name="GM3H"/>.

=Structure=
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central antiparallel four-stranded <scene name='78/781960/Beta_sheet/1'>ß-sheet</scene> with two α-helices running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.
[[Image:Hrp1 structure cropped for protopedia.png|350 px|left|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element. Notice the interface between the ß-sheets of Hrp1 and the RNA.]]
==Hrp1-RNA interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA bases. Only six RNA bases, an (AU)3 repeat, act as the PEE and form specific contacts with Hrp1. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue). In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds.

=Relevance=

==Relationships to other proteins==
The RNP-type RBD is found in many proteins involved in post-transcriptional pre-mRNA processing (5' end capping, splicing, 3' end polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>.

==Interaction with RNA15==

=References=
<references/>
1. Pérez-Cañadillas, J. Grabbing The Message: Structural Basis Of Mrna 3′UTR Recognition By Hrp1. The EMBO Journal 2006, 25, 3167-3178.
2. Cléry, A.; Blatter, M.; Allain, F. RNA Recognition Motifs: Boring? Not Quite. Current Opinion in Structural Biology 2008, 18, 290-298.
3. Guo, Z.; Sherman, F. 3′-End-Forming Signals Of Yeast Mrna. Trends in Biochemical Sciences 1996, 21, 477-481.
4. Kessler, M.; Henry, M.; Shen, E.; Zhao, J.; Gross, S.; Silver, P.; Moore, C. Hrp1, A Sequence-Specific RNA-Binding Protein That Shuttles Between The Nucleus And The Cytoplasm, Is Required For Mrna 3'-End Formation In Yeast. Genes & Development 1997, 11, 2545-2556.
5. Leeper, T.; Qu, X.; Lu, C.; Moore, C.; Varani, G. Novel Protein–Protein Contacts Facilitate Mrna 3′-Processing Signal Recognition By Rna15 And Hrp1. Journal of Molecular Biology 2010, 401, 334-349.
6. The PyMol Molecular Graphics System, Version 2.0 Schrödinger, LLC. (for structural depictions)

User:Matthew Douglas Moore/Sandbox 1

2018-03-27T23:24:32Z

Matthew Douglas Moore:

=Introduction=
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='Insert optional scene name here' />
Hrp1 is a [https://en.wikipedia.org/wiki/Polyadenylation polyadenylation] factor found in Saccharomyces cervisiae (yeast) <ref name="GM3H">PMID: 16794580</ref>. This protein recognizes and binds to an RNA sequence in the [https://en.wikipedia.org/wiki/Three_prime_untranslated_region 3'UTR] called the polyadenylation enhancement element (PEE) <ref name="GM3H"/>.

=Structure=
Hrp1 is a single strand [https://en.wikipedia.org/wiki/RNA-binding_protein RNA-binding protein] composed of two RNP-type [https://en.wikipedia.org/wiki/RNA_recognition_motif RNA-binding domains (RBDs)] arranged in tandem with a typical ßαßßαß architecture <ref name="GM3H"/>. The two RBDs have similar topolgies, both containing a central antiparallel four-stranded <scene name='78/781960/Beta_sheet/1'>ß-sheet</scene> with two α-helices running across one face <ref name="GM3H"/>. The two RBDs associate to form a deep and positively charged <scene name='78/781960/Hrp1-rna_interface_surface/2'>cleft</scene>, which constitutes the binding site for the RNA molecule <ref name="GM3H"/>.
[[Image:Hrp1 structure cropped for protopedia.png|350 px|left|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element. Notice the interface between the ß-sheets of Hrp1 and the RNA.]]
==Hrp1-RNA interactions==
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA bases. Only six RNA bases, an (AU)3 repeat, act as the PEE and form specific contacts with Hrp1. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue). In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds.

=Relevance=

==Relationships to other proteins==
The RNP-type RBD is found in many proteins involved in post-transcriptional pre-mRNA processing (5' end capping, splicing, 3' end polyadenylation, and transport from the nucleus)<ref name="RRMB">PMID: 18515081</ref>.

==Interaction with RNA15==

=References=
<references/>
1. Pérez-Cañadillas, J. Grabbing The Message: Structural Basis Of Mrna 3′UTR Recognition By Hrp1. The EMBO Journal 2006, 25, 3167-3178.
2. Cléry, A.; Blatter, M.; Allain, F. RNA Recognition Motifs: Boring? Not Quite. Current Opinion in Structural Biology 2008, 18, 290-298.
3. Guo, Z.; Sherman, F. 3′-End-Forming Signals Of Yeast Mrna. Trends in Biochemical Sciences 1996, 21, 477-481.
4. Kessler, M.; Henry, M.; Shen, E.; Zhao, J.; Gross, S.; Silver, P.; Moore, C. Hrp1, A Sequence-Specific RNA-Binding Protein That Shuttles Between The Nucleus And The Cytoplasm, Is Required For Mrna 3'-End Formation In Yeast. Genes & Development 1997, 11, 2545-2556.
5. Leeper, T.; Qu, X.; Lu, C.; Moore, C.; Varani, G. Novel Protein–Protein Contacts Facilitate Mrna 3′-Processing Signal Recognition By Rna15 And Hrp1. Journal of Molecular Biology 2010, 401, 334-349.
6. The PyMol Molecular Graphics System, Version 2.0 Schrödinger, LLC. (for structural depictions)

User:Matthew Douglas Moore/Sandbox 1

2018-03-27T16:30:18Z

Matthew Douglas Moore:

CODE

=Introduction=
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='Insert optional scene name here' />
Hrp1 is a polyadenylation factor found in Saccharomyces cervisiae (yeast).

==Relationships to other proteins==

=Structure=
Hrp1 is composed of two RNP-type RNA-binding domains (RBDs) arranged in tandem with a typical ßαßßαß architecture. The two RBDs have similar topolgies, both containing a central antiparallel four-stranded <scene name='78/781960/Beta_sheet/1'>ß-sheet</scene> with two α-helices running across one face.
[[Image:Hrp1 structure cropped for protopedia.png|350 px|left|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element. Notice the interface between the ß-sheets of Hrp1 and the RNA.]]
==Hrp1-RNA interactions==
The <scene name='78/781960/Hrp1-rna_interface_surface/2'>interface</scene> between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA bases. Only six RNA bases, (AU)3, form specific contacts with Hrp1. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue). In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds.

<scene name='78/781945/Interaction_between_domains/5'>Interaction between RRM domains</scene>

<scene name='78/781945/Linker_rna/1'>Interaction between linker and RNA</scene>

=Relevance=

=References=
1. Pérez-Cañadillas, J. Grabbing The Message: Structural Basis Of Mrna 3′UTR Recognition By Hrp1. The EMBO Journal 2006, 25, 3167-3178.
2. Cléry, A.; Blatter, M.; Allain, F. RNA Recognition Motifs: Boring? Not Quite. Current Opinion in Structural Biology 2008, 18, 290-298.
3. Guo, Z.; Sherman, F. 3′-End-Forming Signals Of Yeast Mrna. Trends in Biochemical Sciences 1996, 21, 477-481.
4. Kessler, M.; Henry, M.; Shen, E.; Zhao, J.; Gross, S.; Silver, P.; Moore, C. Hrp1, A Sequence-Specific RNA-Binding Protein That Shuttles Between The Nucleus And The Cytoplasm, Is Required For Mrna 3'-End Formation In Yeast. Genes & Development 1997, 11, 2545-2556.
5. Leeper, T.; Qu, X.; Lu, C.; Moore, C.; Varani, G. Novel Protein–Protein Contacts Facilitate Mrna 3′-Processing Signal Recognition By Rna15 And Hrp1. Journal of Molecular Biology 2010, 401, 334-349.
6. The PyMol Molecular Graphics System, Version 2.0 Schrödinger, LLC. (for structural depictions)
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-27T16:29:54Z

Matthew Douglas Moore:

=Introduction=
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='78/781945/Hrp1 and PEE/1'>Default</scene>' />
Hrp1 is a polyadenylation factor found in Saccharomyces cervisiae (yeast).

==Relationships to other proteins==

=Structure=
Hrp1 is composed of two RNP-type RNA-binding domains (RBDs) arranged in tandem with a typical ßαßßαß architecture. The two RBDs have similar topolgies, both containing a central antiparallel four-stranded <scene name='78/781960/Beta_sheet/1'>ß-sheet</scene> with two α-helices running across one face.
[[Image:Hrp1 structure cropped for protopedia.png|350 px|left|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element. Notice the interface between the ß-sheets of Hrp1 and the RNA.]]
==Hrp1-RNA interactions==
The <scene name='78/781960/Hrp1-rna_interface_surface/2'>interface</scene> between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA bases. Only six RNA bases, (AU)3, form specific contacts with Hrp1. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue). In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds.

<scene name='78/781945/Interaction_between_domains/5'>Interaction between RRM domains</scene>

<scene name='78/781945/Linker_rna/1'>Interaction between linker and RNA</scene>

<scene name='78/781945/Protein_domains/2'>RBDs and Linker</scene>

=Relevance=

=References=
1. Pérez-Cañadillas, J. Grabbing The Message: Structural Basis Of Mrna 3′UTR Recognition By Hrp1. The EMBO Journal 2006, 25, 3167-3178.
2. Cléry, A.; Blatter, M.; Allain, F. RNA Recognition Motifs: Boring? Not Quite. Current Opinion in Structural Biology 2008, 18, 290-298.
3. Guo, Z.; Sherman, F. 3′-End-Forming Signals Of Yeast Mrna. Trends in Biochemical Sciences 1996, 21, 477-481.
4. Kessler, M.; Henry, M.; Shen, E.; Zhao, J.; Gross, S.; Silver, P.; Moore, C. Hrp1, A Sequence-Specific RNA-Binding Protein That Shuttles Between The Nucleus And The Cytoplasm, Is Required For Mrna 3'-End Formation In Yeast. Genes & Development 1997, 11, 2545-2556.
5. Leeper, T.; Qu, X.; Lu, C.; Moore, C.; Varani, G. Novel Protein–Protein Contacts Facilitate Mrna 3′-Processing Signal Recognition By Rna15 And Hrp1. Journal of Molecular Biology 2010, 401, 334-349.
6. The PyMol Molecular Graphics System, Version 2.0 Schrödinger, LLC. (for structural depictions)
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-27T15:56:50Z

Matthew Douglas Moore:

CODE

=Introduction=
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='Insert optional scene name here' />
Hrp1 is a polyadenylation factor found in Saccharomyces cervisiae (yeast).

==Relationships to other proteins==

=Structure=
Hrp1 is composed of two RNP-type RNA-binding domains (RBDs) arranged in tandem with a typical ßαßßαß architecture. The two RBDs have similar topolgies, both containing a central antiparallel four-stranded <scene name='78/781960/Beta_sheet/1'>ß-sheet</scene> with two α-helices running across one face.
[[Image:Hrp1 structure cropped for protopedia.png|350 px|left|thumb|Figure 1: Cartoon representation of the Hrp1-PEE complex. The RNA is shown as a stick model and is colored by element. Notice the interface between the ß-sheets of Hrp1 and the RNA.]]
==Hrp1-RNA interactions==
The <scene name='78/781960/Hrp1-rna_interface_surface/2'>interface</scene> between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA bases. Only six RNA bases, (AU)3, form specific contacts with Hrp1. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding. Most of the key residues that interact with the RNA can be found in the ß-sheet region of Hrp1; however, loops and the interdomain linker are also essential for Hrp1-RNA recognition. Perhaps the most important Hrp1-RNA interaction is the <scene name='78/781960/Hrp1_scene_ade4trp168/2'>interaction between Ade4 and Trp168</scene> (a conserved residue). In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds.

<scene name='78/781945/Interaction_between_domains/5'>Interaction between RRM domains</scene>

<scene name='78/781945/Linker_rna/1'>Interaction between linker and RNA</scene>

<scene name='78/781945/Protein_domains/2'>RBDs and Linker</scene>

=Relevance=

=References=
1. Pérez-Cañadillas, J. Grabbing The Message: Structural Basis Of Mrna 3′UTR Recognition By Hrp1. The EMBO Journal 2006, 25, 3167-3178.
2. Cléry, A.; Blatter, M.; Allain, F. RNA Recognition Motifs: Boring? Not Quite. Current Opinion in Structural Biology 2008, 18, 290-298.
3. Guo, Z.; Sherman, F. 3′-End-Forming Signals Of Yeast Mrna. Trends in Biochemical Sciences 1996, 21, 477-481.
4. Kessler, M.; Henry, M.; Shen, E.; Zhao, J.; Gross, S.; Silver, P.; Moore, C. Hrp1, A Sequence-Specific RNA-Binding Protein That Shuttles Between The Nucleus And The Cytoplasm, Is Required For Mrna 3'-End Formation In Yeast. Genes & Development 1997, 11, 2545-2556.
5. Leeper, T.; Qu, X.; Lu, C.; Moore, C.; Varani, G. Novel Protein–Protein Contacts Facilitate Mrna 3′-Processing Signal Recognition By Rna15 And Hrp1. Journal of Molecular Biology 2010, 401, 334-349.
6. The PyMol Molecular Graphics System, Version 2.0 Schrödinger, LLC. (for structural depictions)
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-27T15:07:32Z

Matthew Douglas Moore:

User:Matthew Douglas Moore/Sandbox 1

2018-03-26T21:09:48Z

Matthew Douglas Moore:

==Hrp1==
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='Insert optional scene name here' />
This is a default text for your page '''Cory A. Wuerch/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
[[Image:hrp1_image1.png|100 px|left|thumb|Figure Legend]]

== Function ==

== Disease ==
This protein is not known to be related to any diseases.
== Relevance ==

= Structure =

== Structural highlights ==

<scene name='78/781960/Hrp1_scene1/1'>hrp1_scene1</scene>

<scene name='78/781960/Hrp1_scene1/3'>Zoomed out scene</scene>

<scene name='78/781960/Hrp1_scene_ade4trp168/2'>Interaction between Ade4 and Trp168</scene>

<scene name='78/781945/Interaction_between_domains/5'>Interaction between RRM domains</scene>

<scene name='78/781945/Linker_rna/1'>Interaction between linker and RNA</scene>

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-26T20:26:47Z

Matthew Douglas Moore:

==Hrp1==
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='Insert optional scene name here' />
This is a default text for your page '''Cory A. Wuerch/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
[[Image:hrp1_image1.png|100 px|left|thumb|Figure Legend]]

== Function ==

== Disease ==
This protein is not known to be related to any diseases.
== Relevance ==

= Structure =

== Structural highlights ==

<scene name='78/781960/Hrp1_scene1/1'>hrp1_scene1</scene>

<scene name='78/781960/Hrp1_scene1/3'>Zoomed out scene</scene>

<scene name='78/781960/Hrp1_scene_ade4trp168/2'>Interaction between Ade4 and Trp168</scene>

<scene name='78/781945/Interaction_between_domains/5'>Interaction between RRM domains</scene>

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-26T20:19:25Z

Matthew Douglas Moore:

==Hrp1==
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='Insert optional scene name here' />
This is a default text for your page '''Cory A. Wuerch/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
[[Image:hrp1_image1.png|100 px|left|thumb|Figure Legend]]

== Function ==

== Disease ==
This protein is not known to be related to any diseases.
== Relevance ==

= Structure =

== Structural highlights ==

<scene name='78/781960/Hrp1_scene1/1'>hrp1_scene1</scene>

<scene name='78/781960/Hrp1_scene1/3'>Zoomed out scene</scene>

<scene name='78/781960/Hrp1_scene_ade4trp168/2'>Interaction between Ade4 and Trp168</scene>

<scene name='78/781945/Interaction_between_domains/1'>TextToBeDisplayed</scene>

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-20T16:45:39Z

Matthew Douglas Moore:

==Hrp1==
<Structure load='2cjk' size='350' frame='true' align='right' caption='Hrp1' scene='Insert optional scene name here' />
This is a default text for your page '''Cory A. Wuerch/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
[[Image:hrp1_image1.png|100 px|left|thumb|Figure Legend]]

== Function ==

== Disease ==
This protein is not known to be related to any diseases.
== Relevance ==

= Structure =

== Structural highlights ==

<scene name='78/781960/Hrp1_scene1/1'>hrp1_scene1</scene>

<scene name='78/781960/Hrp1_scene1/3'>Zoomed out scene</scene>

<scene name='78/781960/Hrp1_scene_ade4trp168/2'>Interaction between Ade4 and Trp168</scene>

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-06T17:19:32Z

Matthew Douglas Moore:

==Hrp1 (''Saccharomyces cerevisiae'')==
[[Image:pastedImage0.png |100 px|left|thumb|Figure Legend]]
<Structure load='2cjk' size='350' frame='true' align='right' caption='2cjk' scene='Insert optional scene name here' />

== Relations to Other Proteins==

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-06T17:18:39Z

Matthew Douglas Moore:

==Hrp1 (''Saccharomyces cerevisiae'')==
[[Image:pastedImage0.png |100 px|left|thumb|Figure Legend]]
<Structure load='2cjk' size='350' frame='true' align='right' caption='2cjk' scene='Insert optional scene name here' />
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Matthew Douglas Moore/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Relations to Other Proteins==

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-06T16:48:59Z

Matthew Douglas Moore:

==Hrp1 (''Saccharomyces cerevisiae'')==
[[Image:pastedImage0.png |100 px|left|thumb|Figure Legend]]
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Matthew Douglas Moore/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Relations to Other Proteins==

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

File:PastedImage0.png

2018-03-06T16:41:27Z

Matthew Douglas Moore:

User:Matthew Douglas Moore/Sandbox 1

2018-03-06T16:36:14Z

Matthew Douglas Moore:

==Hrp1 (''Saccharomyces cerevisiae'')==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Matthew Douglas Moore/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Relations to Other Proteins==

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-06T16:33:06Z

Matthew Douglas Moore:

==Hrp1 (''Saccharomyces cerevisiae'')==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Matthew Douglas Moore/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-06T16:30:47Z

Matthew Douglas Moore:

==Hrp1 (Saccharomyces cerevisiae)==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Matthew Douglas Moore/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Matthew Douglas Moore/Sandbox 1

2018-03-06T16:16:54Z

Matthew Douglas Moore: New page: ==Your Heading Here (maybe something like 'Structure')== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for you...

==Your Heading Here (maybe something like 'Structure')==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Matthew Douglas Moore/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Matthew Douglas Moore

2018-03-06T16:15:23Z

Matthew Douglas Moore:

* Full Real Name: Matthew Douglas Moore

* Position: Undergraduate Student

* Institution (NO ABBREVIATIONS): Butler University

* City, State/Province, Country: Indianapolis, Indiana, United States of America

* Field of Expertise or Study: Chemistry

[[User:Matthew Douglas Moore/Sandbox 1]]