Structural basis for spumavirus GAG tethering to chromatin
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Paul Lesbats Erik Serrao Daniel P Maskell Val Pye Nicola O'Reilly Dirk Lindemann Alan N Engelman Peter CherepanovAbstract
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.
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Volume 114
Issue number 21
Pages 5509-5514
Available online
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Publisher website (DOI) 10.1073/pnas.1621159114
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Europe PubMed Central 28490494
Pubmed 28490494
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