Structural basis for spumavirus GAG tethering to chromatin

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Paul Lesbats - , The Francis Crick Institute (Autor:in)
  • Erik Serrao - , Dana-Farber Cancer Institute (Autor:in)
  • Daniel P Maskell - , The Francis Crick Institute (Autor:in)
  • Valerie E Pye - , The Francis Crick Institute (Autor:in)
  • Nicola O'Reilly - , The Francis Crick Institute (Autor:in)
  • Dirk Lindemann - , Institut für Medizinische Mikrobiologie und Virologie (Autor:in)
  • Alan N Engelman - , Dana-Farber Cancer Institute (Autor:in)
  • Peter Cherepanov - , The Francis Crick Institute (Autor:in)

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)5509-5514
Seitenumfang6
FachzeitschriftProceedings of the National Academy of Sciences of the United States of America : PNAS
Jahrgang114
Ausgabenummer21
PublikationsstatusVeröffentlicht - 23 Mai 2017
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC5448199
ORCID /0000-0002-0320-4223/work/150884999
Scopus 85019556762

Schlagworte

Schlagwörter

  • Histones/metabolism, Nucleosomes/metabolism, Spumavirus/physiology, Virus Integration