The structure of HIV-1 Rev filaments suggests a bilateral model for Rev-RRE assembly

DOI: 10.1016/j.str.2016.04.015

Authors: Mike Dimattia (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health) , Norman R. Watts (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health) , Naiqian Cheng (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health) , Rick Huang (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health) , J. Bernard Heymann (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health) , Jonathan Grimes (University of Oxford; Diamond Light Source) , Paul T. Wingfield (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health) , David I. Stuart (University of Oxford; Diamond Light Source) , Alasdair C. Steven (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure , VOL 24 , PAGES 1068 - 1080

State: Published (Approved)
Published: July 2016

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 15nm 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.

Diamond Keywords: Human Immunodeficiency Virus (HIV); Viruses

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I02-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Other Facilities: ID23-EH2 at ESRF

Added On: 15/08/2016 10:50

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)