Structural basis for retroviral integration into nucleosomes

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Daniel P Maskell - , The Francis Crick Institute (Autor:in)
  • Ludovic Renault - , The Francis Crick Institute (Autor:in)
  • Erik Serrao - , Dana-Farber Cancer Institute (Autor:in)
  • Paul Lesbats - , The Francis Crick Institute (Autor:in)
  • Rishi Matadeen - , NeCEN (Autor:in)
  • Stephen Hare - , Imperial College London (Autor:in)
  • Dirk Lindemann - , Institut für Medizinische Mikrobiologie und Virologie, Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Alan N Engelman - , Dana-Farber Cancer Institute (Autor:in)
  • Alessandro Costa - , The Francis Crick Institute (Autor:in)
  • Peter Cherepanov - , Imperial College London (Autor:in)

Abstract

Retroviral integration is catalysed by a tetramer of integrase (IN) assembled on viral DNA ends in a stable complex, known as the intasome. How the intasome interfaces with chromosomal DNA, which exists in the form of nucleosomal arrays, is currently unknown. Here we show that the prototype foamy virus (PFV) intasome is proficient at stable capture of nucleosomes as targets for integration. Single-particle cryo-electron microscopy reveals a multivalent intasome-nucleosome interface involving both gyres of nucleosomal DNA and one H2A-H2B heterodimer. While the histone octamer remains intact, the DNA is lifted from the surface of the H2A-H2B heterodimer to allow integration at strongly preferred superhelix location ±3.5 positions. Amino acid substitutions disrupting these contacts impinge on the ability of the intasome to engage nucleosomes in vitro and redistribute viral integration sites on the genomic scale. Our findings elucidate the molecular basis for nucleosome capture by the viral DNA recombination machinery and the underlying nucleosome plasticity that allows integration.

Details

OriginalspracheEnglisch
Seiten (von - bis)366-9
Seitenumfang4
FachzeitschriftNature
Jahrgang523
Ausgabenummer7560
PublikationsstatusVeröffentlicht - 16 Juli 2015
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC4530500
ORCID /0000-0002-0320-4223/work/150885017
Scopus 84928916966

Schlagworte

Schlagwörter

  • Amino Acid Substitution, Binding Sites/genetics, Cryoelectron Microscopy, DNA/genetics, Genome/genetics, Histones/chemistry, Integrases/metabolism, Models, Molecular, Nucleosomes/chemistry, Protein Multimerization, Recombination, Genetic, Spumavirus/chemistry, Virus Integration