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

2016; Elsevier BV; Volume: 24; Issue: 7 Linguagem: Inglês

10.1016/j.str.2016.04.015

1878-4186

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

HIV Research and Treatment

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.