Retroviral prototype foamy virus intasome binding to a nucleosome target does not determine integration efficiency.
enzyme catalysis
integration
nucleosome
protein–protein interaction
prototype foamy virus
retrovirus
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
Historique:
received:
07
12
2020
revised:
12
03
2021
accepted:
16
03
2021
pubmed:
22
3
2021
medline:
24
8
2021
entrez:
21
3
2021
Statut:
ppublish
Résumé
Retroviral integrases must navigate host DNA packaged as chromatin during integration of the viral genome. Prototype foamy virus (PFV) integrase (IN) forms a tetramer bound to two viral DNA (vDNA) ends in a complex termed an intasome. PFV IN consists of four domains: the amino terminal extension domain (NED), amino terminal domain (NTD), catalytic core domain (CCD), and carboxyl terminal domain (CTD). The domains of the two inner IN protomers have been visualized, as well as the CCDs of the two outer IN protomers. However, the roles of the amino and carboxyl terminal domains of the PFV intasome outer subunits during integration to a nucleosome target substrate are not clear. We used the well-characterized 601 nucleosome to assay integration activity as well as intasome binding. PFV intasome integration to 601 nucleosomes occurs in clusters at four independent sites. We find that the outer protomer NED and NTD domains have no significant effects on integration efficiency, site selection, or binding. The CTDs of the outer PFV intasome subunits dramatically affect nucleosome binding but have little effect on total integration efficiency. The outer PFV IN CTDs did significantly alter the integration efficiency at one site. Histone tails also significantly affect intasome binding, but have little impact on PFV integration efficiency or site selection. These results indicate that binding to nucleosomes does not correlate with integration efficiency and suggests most intasome-binding events are unproductive.
Identifiants
pubmed: 33744295
pii: S0021-9258(21)00328-8
doi: 10.1016/j.jbc.2021.100550
pmc: PMC8050864
pii:
doi:
Substances chimiques
Chromatin
0
DNA, Viral
0
Histones
0
Nucleosomes
0
Viral Proteins
0
Integrases
EC 2.7.7.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
100550Subventions
Organisme : NIAID NIH HHS
ID : R01 AI126742
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI099854
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
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