| Literature DB >> 28059770 |
Allison Ballandras-Colas1, Daniel P Maskell1, Erik Serrao2,3, Julia Locke4, Paolo Swuec4, Stefán R Jónsson5, Abhay Kotecha6, Nicola J Cook1, Valerie E Pye1, Ian A Taylor7, Valgerdur Andrésdóttir5, Alan N Engelman2,3, Alessandro Costa4, Peter Cherepanov1,8.
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.Entities:
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Year: 2017 PMID： 28059770 PMCID： PMC5321526 DOI： 10.1126/science.aah7002
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728