2x7l

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{{STRUCTURE_2x7l| PDB=2x7l | SCENE= }}
 
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===Implications of the HIV-1 Rev dimer structure at 3.2A resolution for multimeric binding to the Rev response element===
 
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{{ABSTRACT_PUBMED_20231488}}
 
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==Function==
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==Implications of the HIV-1 Rev dimer structure at 3.2A resolution for multimeric binding to the Rev response element==
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[[http://www.uniprot.org/uniprot/REV_HV1B1 REV_HV1B1]] Escorts unspliced or incompletely spliced viral pre-mRNAs (late transcripts) out of the nucleus of infected cells. These pre-mRNAs carry a recognition sequence called Rev responsive element (RRE) located in the env gene, that is not present in fully spliced viral mRNAs (early transcripts). This function is essential since most viral proteins are translated from unspliced or partially spliced pre-mRNAs which cannot exit the nucleus by the pathway used by fully processed cellular mRNAs. Rev itself is translated from a fully spliced mRNA that readily exits the nucleus. Rev's nuclear localization signal (NLS) binds directly to KPNB1/Importin beta-1 without previous binding to KPNA1/Importin alpha-1. KPNB1 binds to the GDP bound form of RAN (Ran-GDP) and targets Rev to the nucleus. In the nucleus, the conversion from Ran-GDP to Ran-GTP dissociates Rev from KPNB1 and allows Rev's binding to the RRE in viral pre-mRNAs. Rev multimerization on the RRE via cooperative assembly exposes its nuclear export signal (NES) to the surface. Rev can then form a complex with XPO1/CRM1 and Ran-GTP, leading to nuclear export of the complex. Conversion from Ran-GTP to Ran-GDP mediates dissociation of the Rev/RRE/XPO1/RAN complex, so that Rev can return to the nucleus for a subsequent round of export. Beside KPNB1, also seems to interact with TNPO1/Transportin-1, RANBP5/IPO5 and IPO7/RANBP7 for nuclear import. The nucleoporin-like HRB/RIP is an essential cofactor that probably indirectly interacts with Rev to release HIV RNAs from the perinuclear region to the cytoplasm (By similarity).
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<StructureSection load='2x7l' size='340' side='right'caption='[[2x7l]], [[Resolution|resolution]] 3.17&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2x7l]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_BH10 Human immunodeficiency virus type 1 BH10] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X7L FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.17&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2x7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x7l OCA], [https://pdbe.org/2x7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x7l RCSB], [https://www.ebi.ac.uk/pdbsum/2x7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x7l ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/REV_HV1B1 REV_HV1B1] Escorts unspliced or incompletely spliced viral pre-mRNAs (late transcripts) out of the nucleus of infected cells. These pre-mRNAs carry a recognition sequence called Rev responsive element (RRE) located in the env gene, that is not present in fully spliced viral mRNAs (early transcripts). This function is essential since most viral proteins are translated from unspliced or partially spliced pre-mRNAs which cannot exit the nucleus by the pathway used by fully processed cellular mRNAs. Rev itself is translated from a fully spliced mRNA that readily exits the nucleus. Rev's nuclear localization signal (NLS) binds directly to KPNB1/Importin beta-1 without previous binding to KPNA1/Importin alpha-1. KPNB1 binds to the GDP bound form of RAN (Ran-GDP) and targets Rev to the nucleus. In the nucleus, the conversion from Ran-GDP to Ran-GTP dissociates Rev from KPNB1 and allows Rev's binding to the RRE in viral pre-mRNAs. Rev multimerization on the RRE via cooperative assembly exposes its nuclear export signal (NES) to the surface. Rev can then form a complex with XPO1/CRM1 and Ran-GTP, leading to nuclear export of the complex. Conversion from Ran-GTP to Ran-GDP mediates dissociation of the Rev/RRE/XPO1/RAN complex, so that Rev can return to the nucleus for a subsequent round of export. Beside KPNB1, also seems to interact with TNPO1/Transportin-1, RANBP5/IPO5 and IPO7/RANBP7 for nuclear import. The nucleoporin-like HRB/RIP is an essential cofactor that probably indirectly interacts with Rev to release HIV RNAs from the perinuclear region to the cytoplasm (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/x7/2x7l_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2x7l ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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HIV-1 Rev is a small regulatory protein that mediates the nuclear export of viral mRNAs, an essential step in the HIV replication cycle. In this process Rev oligomerizes in association with a highly structured RNA motif, the Rev response element. Crystallographic studies of Rev have been hampered by the protein's tendency to aggregate, but Rev has now been found to form a stable soluble equimolar complex with a specifically engineered monoclonal Fab fragment. We have determined the structure of this complex at 3.2 A resolution. It reveals a molecular dimer of Rev, bound on either side by a Fab, where the ordered portion of each Rev monomer (residues 9-65) contains two coplanar alpha-helices arranged in hairpin fashion. Subunits dimerize through overlapping of the hairpin prongs. Mating of hydrophobic patches on the outer surface of the dimer is likely to promote higher order interactions, suggesting a model for Rev oligomerization onto the viral RNA.
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==About this Structure==
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Implications of the HIV-1 Rev dimer structure at 3.2 A resolution for multimeric binding to the Rev response element.,Dimattia MA, Watts NR, Stahl SJ, Rader C, Wingfield PT, Stuart DI, Steven AC, Grimes JM Proc Natl Acad Sci U S A. 2010 Mar 15. PMID:20231488<ref>PMID:20231488</ref>
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[[2x7l]] is a 18 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_3 Human immunodeficiency virus 3] and [http://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X7L OCA].
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==See Also==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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*[[Antibody|Antibody]]
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</div>
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<div class="pdbe-citations 2x7l" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:020231488</ref><references group="xtra"/><references/>
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*[[Antibody 3D structures|Antibody 3D structures]]
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[[Category: Human immunodeficiency virus 3]]
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*[[Protein Rev|Protein Rev]]
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[[Category: Unidentified]]
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*[[3D structures of human antibody|3D structures of human antibody]]
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[[Category: DiMattia, M A.]]
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== References ==
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[[Category: Grimes, J M.]]
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<references/>
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[[Category: Rader, C.]]
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__TOC__
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[[Category: Stahl, S J.]]
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</StructureSection>
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[[Category: Steven, A C.]]
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[[Category: Human immunodeficiency virus type 1 BH10]]
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[[Category: Stuart, D I.]]
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[[Category: Large Structures]]
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[[Category: Watts, N R.]]
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[[Category: Synthetic construct]]
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[[Category: Wingfield, P T.]]
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[[Category: DiMattia MA]]
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[[Category: Immune system]]
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[[Category: Grimes JM]]
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[[Category: Nuclear export]]
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[[Category: Rader C]]
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[[Category: Post-transcriptional regulation]]
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[[Category: Stahl SJ]]
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[[Category: Steven AC]]
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[[Category: Stuart DI]]
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[[Category: Watts NR]]
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[[Category: Wingfield PT]]

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Implications of the HIV-1 Rev dimer structure at 3.2A resolution for multimeric binding to the Rev response element

PDB ID 2x7l

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