5m0q
Cryo-EM reconstruction of the maedi-visna virus (MVV) intasomeCryo-EM reconstruction of the maedi-visna virus (MVV) intasome
Structural highlights
Function[POL_VILVK] During replicative cycle of retroviruses, the reverse-transcribed viral DNA is integrated into the host chromosome by the viral integrase enzyme. RNase H activity is associated with the reverse transcriptase. Publication Abstract from PubMedRetroviral 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. A supramolecular assembly mediates lentiviral DNA integration.,Ballandras-Colas A, Maskell DP, Serrao E, Locke J, Swuec P, Jonsson SR, Kotecha A, Cook NJ, Pye VE, Taylor IA, Andresdottir V, Engelman AN, Costa A, Cherepanov P Science. 2017 Jan 6;355(6320):93-95. doi: 10.1126/science.aah7002. PMID:28059770[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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