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dc.contributor.author Ballandras-Colas, Allison
dc.contributor.author Brown, Monica
dc.contributor.author Cook, Nicola J.
dc.contributor.author Dewdney, Tamaria G.
dc.contributor.author Demeler, Borries
dc.contributor.author Cherepanov, Peter
dc.contributor.author Lyumkis, Dmitry
dc.contributor.author Engelman, Alan N.
dc.date.accessioned 2021-10-20T19:06:35Z
dc.date.available 2021-10-20T19:06:35Z
dc.date.issued 2016
dc.identifier.citation Ballandras-Colas, A., Brown, M., Cook, N. J., Dewdney, T. G., Demeler, B., Cherepanov, P., Lyumkis, D., & Engelman, A. N. (2016). Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function. Nature, 530, 358-361. https://doi.org/10.1038/nature16955 en_US
dc.identifier.uri https://hdl.handle.net/10133/6067
dc.description Accepted author manuscript en_US
dc.description.abstract Retroviral integrase catalyses the integration of viral DNA into host target DNA, which is an essential step in the life cycle of all retroviruses1. Previous structural characterization of integrase–viral DNA complexes, or intasomes, from the spumavirus prototype foamy virus revealed a functional integrase tetramer2,3,4,5, and it is generally believed that intasomes derived from other retroviral genera use tetrameric integrase6,7,8,9. However, the intasomes of orthoretroviruses, which include all known pathogenic species, have not been characterized structurally. Here, using single-particle cryo-electron microscopy and X-ray crystallography, we determine an unexpected octameric integrase architecture for the intasome of the betaretrovirus mouse mammary tumour virus. The structure is composed of two core integrase dimers, which interact with the viral DNA ends and structurally mimic the integrase tetramer of prototype foamy virus, and two flanking integrase dimers that engage the core structure via their integrase carboxy-terminal domains. Contrary to the belief that tetrameric integrase components are sufficient to catalyse integration, the flanking integrase dimers were necessary for mouse mammary tumour virus integrase activity. The integrase octamer solves a conundrum for betaretroviruses as well as alpharetroviruses by providing critical carboxy-terminal domains to the intasome core that cannot be provided in cis because of evolutionarily restrictive catalytic core domain–carboxy-terminal domain linker regions. The octameric architecture of the intasome of mouse mammary tumour virus provides new insight into the structural basis of retroviral DNA integration. en_US
dc.language.iso en_US en_US
dc.publisher Nature Publishing en_US
dc.subject Cryoelectron microscopy en_US
dc.subject DNA recombination en_US
dc.subject Enzyme mechanisms en_US
dc.subject Retrovirus en_US
dc.subject Betaretroviruses
dc.subject.lcsh Retroviruses
dc.title Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function en_US
dc.type Article en_US
dc.publisher.faculty Arts and Science en_US
dc.publisher.department Department of Chemistry and Biochemistry en_US
dc.description.peer-review Yes en_US
dc.publisher.institution Harvard Medical School en_US
dc.publisher.institution The Salk Institute for Biological Studies en_US
dc.publisher.institution The Francis Crick Institute en_US
dc.publisher.institution University of Texas Health Science Center at San Antonio en_US
dc.publisher.institution Imperial College London en_US
dc.publisher.institution University of Lethbridge en_US
dc.publisher.url https://doi.org/10.1038/nature16955 en_US


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