Details

Autor(en) / Beteiligte

• DiMattia, Michael A.
• Watts, Norman R.
• Cheng, Naiqian
• Huang, Rick
• Heymann, J. Bernard
• Grimes, Jonathan M.
• Wingfield, Paul T.
• Stuart, David I.
• Steven, Alasdair C.

Titel

The Structure of HIV-1 Rev Filaments Suggests a Bilateral Model for Rev-RRE Assembly

Ist Teil von

• Structure (London), 2016-07, Vol.24 (7), p.1068-1080

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• HIV-1 Rev protein mediates the nuclear export of viral RNA genomes. To do so, Rev oligomerizes cooperatively onto an RNA motif, the Rev response element (RRE), forming a complex that engages with the host nuclear export machinery. To better understand Rev oligomerization, we determined four crystal structures of Rev N-terminal domain dimers, which show that they can pivot about their dyad axis, giving crossing angles of 90° to 140°. In parallel, we performed cryoelectron microscopy of helical Rev filaments. Filaments vary from 11 to 15 nm in width, reflecting variations in dimer crossing angle. These structures contain additional density, indicating that C-terminal domains become partially ordered in the context of filaments. This conformational variability may be exploited in the assembly of RRE/Rev complexes. Our data also revealed a third interface between Revs, which offers an explanation for how the arrangement of Rev subunits adapts to the “A”-shaped architecture of the RRE in export-active complexes. [Display omitted] •Rev NTD α-helical hairpins dimerize with widely varying crossing angles•The unfolded CTDs become partially ordered when Rev assembles into helical filaments•Cryo-EM of filaments and crystal structures reveal a novel inter-molecular interface•This interface and variations in crossing angle may help organize Rev-RRE complexes Binding of 8–12 HIV-1 Rev subunits to the RRE of viral transcripts mediates nuclear export. DiMattia et al. describe a novel Rev-Rev interface and the remarkably flexible ways in which Rev can assemble, and propose how this allows Rev to engage with the A-shaped RRE.