A supramolecular assembly mediates lentiviral DNA integration
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Allison Ballandras-Colas Daniel P Maskell Erik Serrao Julia Locke Paolo Swuec Stefán R Jónsson Abhay Kotecha Nicola Cook Val Pye Ian Taylor Valgerdur Andrésdóttir Alan N Engelman Alessandro Costa Peter CherepanovAbstract
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.
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Journal Science
Volume 355
Issue number 6320
Pages 93-95
Available online
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Publisher website (DOI) 10.1126/science.aah7002
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Europe PubMed Central 28059770
Pubmed 28059770
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