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A new HIV-1 Rev structure optimizes interaction with target RNA (RRE) for nuclear export.

Authors :
Watts NR
Eren E
Zhuang X
Wang YX
Steven AC
Wingfield PT
Source :
Journal of structural biology [J Struct Biol] 2018 Aug; Vol. 203 (2), pp. 102-108. Date of Electronic Publication: 2018 Mar 29.
Publication Year :
2018

Abstract

HIV-1 Rev mediates the nuclear export of unspliced and partially-spliced viral transcripts for the production of progeny genomes and structural proteins. In this process, four (or more) copies of Rev assemble onto a highly-structured 351-nt region in such viral transcripts, the Rev response element (RRE). How this occurs is not known. The Rev assembly domain has a helical-hairpin structure which associates through three (A-A, B-B and C-C) interfaces. The RRE has the topology of an upper-case letter A, with the two known Rev binding sites mapping onto the legs of the A. We have determined a crystal structure for the Rev assembly domain at 2.25 Å resolution, without resort to either mutations or chaperones. It shows that B-B dimers adopt an arrangement reversed relative to that previously reported, and join through a C-C interface to form tetramers. The new subunit arrangement shows how four Rev molecules can assemble on the two sites on the RRE to form the specificity checkpoint, and how further copies add through A-A interactions. Residues at the C-C interface, specifically the Pro31-Trp45 axis, are a potential target for intervention.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1095-8657
Volume :
203
Issue :
2
Database :
MEDLINE
Journal :
Journal of structural biology
Publication Type :
Academic Journal
Accession number :
29605570
Full Text :
https://doi.org/10.1016/j.jsb.2018.03.011