Structural basis for spumavirus GAG tethering to chromatin
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Author
Lesbats, Paul
Serrao, Erik
Maskell, Daniel
Pye, Valerie
O’Reilly, Nicola
Lindemann, Dirk
Engelman, Alan
Cherepanov, Peter
Published Version
https://doi.org/10.1073/pnas.1621159114Metadata
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Lesbats, Paul, Erik Serrao, Daniel P. Maskell, Valerie E. Pye, Nicola O’Reilly, Dirk Lindemann, Alan N. Engelman, and Peter Cherepanov. 2017. “Structural Basis for Spumavirus GAG Tethering to Chromatin.” Proceedings of the National Academy of Sciences 114 (21): 5509–14. https://doi.org/10.1073/pnas.1621159114.Abstract
The interactions between a retrovirus and host cell chromatin that underlie integration and provirus expression are poorly understood. The prototype foamy virus (PFV) structural protein GAG associates with chromosomes via a chromatin-binding sequence (CBS) located within its C-terminal region. Here, we show that the PFV CBS is essential and sufficient for a direct interaction with nucleosomes and present a crystal structure of the CBS bound to a mononucleosome. The CBS interacts with the histone octamer, engaging the H2A-H2B acidic patch in a manner similar to other acidic patch-binding proteins such as herpesvirus latency-associated nuclear antigen (LANA). Substitutions of the invariant arginine anchor residue in GAG result in global redistribution of PFV and macaque simian foamy virus (SFVmac) integration sites toward centromeres, dampening the resulting proviral expression without affecting the overall efficiency of integration. Our findings underscore the importance of retroviral structural proteins for integration site selection and the avoidance of genomic junkyards.Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483058
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