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-Structure paper
タイトル | A supramolecular assembly mediates lentiviral DNA integration. |
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ジャーナル・号・ページ | Science, Vol. 355, Issue 6320, Page 93-95, Year 2017 |
掲載日 | 2017年1月6日 |
著者 | Allison Ballandras-Colas / Daniel P Maskell / Erik Serrao / Julia Locke / Paolo Swuec / Stefán R Jónsson / Abhay Kotecha / Nicola J Cook / Valerie E Pye / Ian A Taylor / Valgerdur Andrésdóttir / Alan N Engelman / Alessandro Costa / Peter Cherepanov / |
PubMed 要旨 | 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 ...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. |
リンク | Science / PubMed:28059770 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.78 - 8.2 Å |
構造データ | EMDB-14860: MVV cleaved synaptic complex (CSC) intasome at 4.5 A resolution (re-refined) EMDB-4139, PDB-5m0r: PDB-5llj: PDB-5t3a: |
化合物 | ChemComp-CL: ChemComp-HOH: ChemComp-ACT: ChemComp-MES: |
由来 |
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キーワード | VIRAL PROTEIN / integrase / visna/maedi virus / c-terminal domain / HYDROLASE / retrovirus / lentivirus / DNA-binding / Zn-binding / RNAseH fold / Visna virus integrase / catalytic core domain / intasome / MVV / nucleoprotein complex |