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Structural basis for spumavirus GAG tethering to chromatin

DOI: 10.1073/pnas.1621159114 DOI Help

Authors: Paul Lesbats (The Francis Crick Institute) , Erik Serrao (Dana-Farber Cancer Institute; Harvard Medical School) , Daniel P. Maskell (The Francis Crick Institute) , Valerie E. Pye (The Francis Crick Institute) , Nicola O’reilly (The Francis Crick Institute) , Dirk Lindemann (Technische Universität Dresden) , Alan N. Engelman (Dana-Farber Cancer Institute; The Francis Crick Institute) , Peter Cherepanov (The Francis Crick Institute; Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 114 , PAGES 5509 - 5514

State: Published (Approved)
Published: May 2017
Diamond Proposal Number(s): 9826

Open Access Open Access

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.

Journal Keywords: retrovirus; integration; nucleosome; chromatin-binding

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography

Documents:
5509.full.pdf

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