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4pmi

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Revision as of 17:03, 4 January 2017

Crystal structure of Rev and Rev-response-element RNA complex

Structural highlights

4pmi is a 3 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, ProSAT

Function

[REV_HV1H3] 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.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The HIV-1 protein Rev controls a critical step in viral replication by mediating the nuclear export of unspliced and singly-spliced viral mRNAs. Multiple Rev subunits assemble on the Rev Response Element (RRE), a structured region present in these RNAs, and direct their export through the Crm1 pathway. Rev-RRE assembly occurs via several Rev oligomerization and RNA-binding steps, but how these steps are coordinated to form an export-competent complex is unclear. Here, we report the first crystal structure of a Rev dimer-RRE complex, revealing a dramatic rearrangement of the Rev-dimer upon RRE binding through re-packing of its hydrophobic protein-protein interface. Rev-RNA recognition relies on sequence-specific contacts at the well-characterized IIB site and local RNA architecture at the second site. The structure supports a model in which the RRE utilizes the inherent plasticity of Rev subunit interfaces to guide the formation of a functional complex.

RNA-directed remodeling of the HIV-1 Rev protein orchestrates assembly of the Rev-Rev response element complex.,Jayaraman B, Crosby DC, Homer C, Ribeiro I, Mavor D, Frankel AD Elife. 2014 Dec 8;3. doi: 10.7554/eLife.04120. PMID:25486594^[4]

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

References

↑ Malim MH, Hauber J, Le SY, Maizel JV, Cullen BR. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature. 1989 Mar 16;338(6212):254-7. PMID:2784194 doi:http://dx.doi.org/10.1038/338254a0
↑ Fridell RA, Bogerd HP, Cullen BR. Nuclear export of late HIV-1 mRNAs occurs via a cellular protein export pathway. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4421-4. PMID:8633082
↑ Sanchez-Velar N, Udofia EB, Yu Z, Zapp ML. hRIP, a cellular cofactor for Rev function, promotes release of HIV RNAs from the perinuclear region. Genes Dev. 2004 Jan 1;18(1):23-34. Epub 2003 Dec 30. PMID:14701878 doi:10.1101/gad.1149704
↑ Jayaraman B, Crosby DC, Homer C, Ribeiro I, Mavor D, Frankel AD. RNA-directed remodeling of the HIV-1 Rev protein orchestrates assembly of the Rev-Rev response element complex. Elife. 2014 Dec 8;3. doi: 10.7554/eLife.04120. PMID:25486594 doi:http://dx.doi.org/10.7554/eLife.04120

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Crystal structure of Rev and Rev-response-element RNA complex==
 <StructureSection load='4pmi' size='340' side='right' caption='[[4pmi]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4pmi]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PMI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PMI FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4pmi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pmi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pmi RCSB], [http://www.ebi.ac.uk/pdbsum/4pmi 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=4pmi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pmi OCA], [http://pdbe.org/4pmi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pmi RCSB], [http://www.ebi.ac.uk/pdbsum/4pmi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pmi ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4pmi" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[HIV and accessory proteins|HIV and accessory proteins]]
 == References ==
 <references/>

4pmi

From Proteopedia

Revision as of 17:03, 4 January 2017

Crystal structure of Rev and Rev-response-element RNA complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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