Format

Send to

Choose Destination
Science. 2017 Jan 6;355(6320):93-95. doi: 10.1126/science.aah7002.

A supramolecular assembly mediates lentiviral DNA integration.

Author information

1
Chromatin Structure and Mobile DNA, The Francis Crick Institute, London, NW1 1AT, UK.
2
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
3
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
4
Macromolecular Machines Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
5
Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavik, Iceland.
6
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
7
Macromolecular Structure Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
8
Division of Medicine, Imperial College London, W2 1PG, UK.
#
Contributed equally

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.

PMID:
28059770
PMCID:
PMC5321526
DOI:
10.1126/science.aah7002
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center