Nuclear polyadenylated RNA-binding protein
From Proteopedia
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[[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.]] | [[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== | ==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 <scene name='78/781952/Ua_repeats/1'>(AU)3</scene> 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. 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. | + | The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA bases <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"/>. |
[[Image:Conserved W168 in Hrp1.png|300 px|right|thumb|Figure 2: 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.]] | [[Image:Conserved W168 in Hrp1.png|300 px|right|thumb|Figure 2: 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.]] | ||
Revision as of 01:07, 29 March 2018
Contents |
Introduction
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Hrp1 is a polyadenylation factor found in Saccharomyces cervisiae (yeast) [1]. This protein recognizes and binds to an RNA sequence in the 3'UTR called the polyadenylation enhancement element (PEE) [1].
Structure
Hrp1 is a single strand RNA-binding protein composed of two RNP-type RNA-binding domains (RBDs) arranged in tandem with a typical ßαßßαß architecture [1]. The two RBDs have similar topolgies, both containing a central antiparallel four-stranded with two α-helices running across one face [1]. The two RBDs associate to form a deep and positively charged , which constitutes the binding site for the RNA molecule [1].
Hrp1-RNA Interactions
The interface between Hrp1 and its target RNA sequence is dominated by interactions between key aromatic residues and RNA bases [1]. Only six RNA bases, an repeat, act as the PEE and form specific contacts with Hrp1 [1]. Hydrophilic residues of Hrp1 provide base specificity through hydrogen bonding [1]. 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 [1]. Perhaps the most important Hrp1-RNA interaction is the (a conserved residue) [1]. In this case, Trp168 stacks on Ade4 and forms crucial base-specific hydrogen bonds [1]. It is also worth noting that a second Hrp1 residue is critical to holding Ade4 in place, , which interacts via hydrogen bond with the N1 of Ade4 [1]. A third contributor, , also stacks with Ura7 to aid in RNA recognition and binding [1].
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 . Experimental evidence from the NMR data [1] 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 . Aside from the linker helix, the only interaction between the RBDs is due to 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)[2].
Interaction with RNA15
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 Perez-Canadillas JM. Grabbing the message: structural basis of mRNA 3'UTR recognition by Hrp1. EMBO J. 2006 Jul 12;25(13):3167-78. Epub 2006 Jun 22. PMID:16794580
- ↑ Clery A, Blatter M, Allain FH. RNA recognition motifs: boring? Not quite. Curr Opin Struct Biol. 2008 Jun;18(3):290-8. doi: 10.1016/j.sbi.2008.04.002. PMID:18515081 doi:http://dx.doi.org/10.1016/j.sbi.2008.04.002
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)
Proteopedia Page Contributors and Editors (what is this?)
Cory A. Wuerch, Matthew Douglas Moore, Savannah Davis, Michal Harel, Jaime Prilusky
