A supramolecular assembly mediates lentiviral DNA integration

DOI: 10.1126/science.aah7002

Authors: Allison Ballandras-Colas (The Francis Crick Institute) , Daniel P. Maskell (The Francis Crick Institute) , Erik Serrao (Harvard Medical School; Dana-Farber Cancer Institute) , Julia Locke (The Francis Crick Institute) , Paolo Swuec (The Francis Crick Institute) , Stefán R. Jónsson (University of Iceland) , Abhay Kotecha (University of Oxford) , Nicola J. Cook (The Francis Crick Institute) , Valerie E. Pye (The Francis Crick Institute) , Ian A. Taylor (The Francis Crick Institute) , Valgerdur Andrésdóttir (University of Iceland) , Alan N. Engelman (Dana-Farber Cancer Institute; Harvard Medical School) , Alessandro Costa (The Francis Crick Institute) , Peter Cherepanov (Imperial College London; The Francis Crick Institute)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science , VOL 355 , PAGES 93 - 95

State: Published (Approved)
Published: January 2017
Diamond Proposal Number(s): 13775

Abstract: Retroviral integrase (IN) functions within the intasome nucleoprotein complex to catalyze insertion of viral DNA into cellular chromatin. Using cryo–electron microscopy, we now visualize the functional maedi-visna lentivirus intasome at 4.9 angstrom resolution. The intasome comprises a homo-hexadecamer of IN with a tetramer-of-tetramers architecture featuring eight structurally distinct types of IN protomers supporting two catalytically competent subunits. The conserved intasomal core, previously observed in simpler retroviral systems, is formed between two IN tetramers, with a pair of C-terminal domains from flanking tetramers completing the synaptic interface. Our results explain how HIV-1 IN, which self-associates into higher-order multimers, can form a functional intasome, reconcile the bulk of early HIV-1 IN biochemical and structural data, and provide a lentiviral platform for design of HIV-1 IN inhibitors.

Diamond Keywords: Human Immunodeficiency Virus (HIV); Viruses

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

Added On: 18/01/2017 13:02

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)