Title
The Structure of HIV-1 Rev Filaments Suggests a Bilateral Model for Rev-RRE Assembly
Author
Michael A. DiMattia, Norman R. Watts, Naiqian Cheng, Rick Huang, J. Bernard Heymann, Jonathan M. Grimes, Paul T. Wingfield, David I. Stuart, Alasdair C. Steven
Year
2016
Journal
Structure
Abstract
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.
Instrument
J-715
Keywords
Circular dichroism, Protein denaturation, Protein folding, Secondary structure, Aggregation, Biochemistry