File(s) under permanent embargo
Structural basis for retroviral integration into nucleosomes
journal contribution
posted on 2023-06-09, 08:01 authored by Daniel P Maskell, Ludovic Renault, Erik Serrao, Paul Lesbats, Rishi Matadeen, Stephen Hare, Dirk Lindemann, Alan N Engelman, Alessandro Costa, Peter CherepanovRetroviral integration is catalysed by a tetramer of integrase (IN) assembled on viral DNA ends in a stable complex, known as the intasome1, 2. 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.
History
Publication status
- Published
File Version
- Published version
Journal
NatureISSN
0028-0836Publisher
Nature Publishing GroupExternal DOI
Issue
7560Volume
523Page range
366-369Department affiliated with
- Biochemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2017-09-22First Compliant Deposit (FCD) Date
2021-03-09Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC