Ballandras-Colas, A, Maskell, DP, Serrao, E et al. (11 more authors) (2017) A supramolecular assembly mediates lentiviral DNA integration. Science, 355 (6320). pp. 93-95. ISSN 0036-8075
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2017, American Association for the Advancement of Science. This is the author's version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science vol. 355 , 6 January 2017, https://doi.org/10.1126/science.aah7002 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 17 Jan 2018 16:04 |
Last Modified: | 21 Mar 2018 19:58 |
Status: | Published |
Publisher: | American Association for the Advancement of Science |
Identification Number: | 10.1126/science.aah7002 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:126324 |