This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4yoe

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 07:37, 7 October 2015

Structure of UP1 bound to RNA 5'-AGU-3'

Structural highlights

4yoe is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[ROA1_HUMAN] Amyotrophic lateral sclerosis;Inclusion body myopathy with Paget disease of bone and frontotemporal dementia. The disease is caused by mutations affecting the gene represented in this entry.^[1] The disease is caused by mutations affecting the gene represented in this entry.^[2]

Function

[ROA1_HUMAN] Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and may modulate splice site selection. May play a role in HCV RNA replication.^[3]

Publication Abstract from PubMed

The heterogeneous nuclear ribonucleoprotein (hnRNP) A1 protein is a multifunctional RNA binding protein implicated in a wide range of biological functions. Mechanisms and putative hnRNP A1-RNA interactions have been inferred primarily from the crystal structure of its UP1 domain bound to ssDNA. RNA stem loops represent an important class of known hnRNP A1 targets, yet little is known about the structural basis of hnRNP A1-RNA recognition. Here, we report the first high-resolution structure (1.92A) of UP1 bound to a 5'-AGU-3' trinucleotide that resembles sequence elements of several native hnRNP A1-RNA stem loop targets. UP1 interacts specifically with the AG dinucleotide sequence via a "nucleobase pocket" formed by the beta-sheet surface of RRM1 and the inter-RRM linker; RRM2 does not contact the RNA. The inter-RRM linker forms the lid of the nucleobase pocket and we show using structure-guided mutagenesis that the conserved salt-bridge interactions (R75:D155 and R88:D157) on the alpha-helical side of the RNA binding surface stabilize the linker in a geometry poised to bind RNA. We further investigated the structural basis of UP1 binding HIViSL3ESS3 by determining a structural model of the complex scored by small-angle X-ray scattering. UP1 docks on the apical loop of SL3ESS3 using its RRM1 domain and inter-RRM linker only. The biophysical implications of the structural model were tested by measuring kinetic binding parameters, where mutations introduced within the apical loop reduce binding affinities by slowing down the rate of complex formation. Collectively, the data presented here provide the first insights into hnRNP A1-RNA interactions.

The First Crystal Structure of the UP1 Domain of hnRNP A1 Bound to RNA Reveals a New Look for an Old RNA Binding Protein.,Morgan CE, Meagher JL, Levengood JD, Delproposto J, Rollins C, Stuckey JA, Tolbert BS J Mol Biol. 2015 May 21. pii: S0022-2836(15)00293-4. doi:, 10.1016/j.jmb.2015.05.009. PMID:26003924^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013 Mar 28;495(7442):467-73. doi: 10.1038/nature11922. Epub 2013 Mar 3. PMID:23455423 doi:http://dx.doi.org/10.1038/nature11922
↑ Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013 Mar 28;495(7442):467-73. doi: 10.1038/nature11922. Epub 2013 Mar 3. PMID:23455423 doi:http://dx.doi.org/10.1038/nature11922
↑ Kim CS, Seol SK, Song OK, Park JH, Jang SK. An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate hepatitis C virus replication. J Virol. 2007 Apr;81(8):3852-65. Epub 2007 Jan 17. PMID:17229681 doi:http://dx.doi.org/10.1128/JVI.01311-06
↑ Morgan CE, Meagher JL, Levengood JD, Delproposto J, Rollins C, Stuckey JA, Tolbert BS. The First Crystal Structure of the UP1 Domain of hnRNP A1 Bound to RNA Reveals a New Look for an Old RNA Binding Protein. J Mol Biol. 2015 May 21. pii: S0022-2836(15)00293-4. doi:, 10.1016/j.jmb.2015.05.009. PMID:26003924 doi:http://dx.doi.org/10.1016/j.jmb.2015.05.009

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4yoe"

@@ Line 4: / Line 4: @@
 <table><tr><td colspan='2'>[[4yoe]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YOE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YOE FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yoe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yoe RCSB], [http://www.ebi.ac.uk/pdbsum/4yoe PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yoe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yoe OCA], [http://pdbe.org/4yoe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yoe RCSB], [http://www.ebi.ac.uk/pdbsum/4yoe PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 18: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4yoe" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 27: / Line 28: @@
 [[Category: Hnrnpa1]]
 [[Category: Protein-rna recognition]]
+[[Category: Rna binding protein-rna complex]]

4yoe

From Proteopedia

Revision as of 07:37, 7 October 2015

Structure of UP1 bound to RNA 5'-AGU-3'

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox