Structural basis for retroviral integration into nucleosomes

Maskell, Daniel P, Renault, Ludovic, Serrao, Erik, Lesbats, Paul, Matadeen, Rishi, Hare, Stephen, Lindemann, Dirk, Engelman, Alan N, Costa, Alessandro and Cherepanov, Peter (2015) Structural basis for retroviral integration into nucleosomes. Nature, 523 (7560). pp. 366-369. ISSN 0028-0836

[img] PDF (For REF only) - Published Version
Restricted to SRO admin only

Download (3MB)


Retroviral 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.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Stephen Hare
Date Deposited: 22 Sep 2017 08:13
Last Modified: 09 Mar 2021 15:30

View download statistics for this item

📧 Request an update