SUMOylation of SAMHD1 at Lysine 595 is required for HIV-1 restriction in non-cycling cells.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 07 2021
28 07 2021
Historique:
received:
16
05
2020
accepted:
05
07
2021
entrez:
29
7
2021
pubmed:
30
7
2021
medline:
5
8
2021
Statut:
epublish
Résumé
SAMHD1 is a cellular triphosphohydrolase (dNTPase) proposed to inhibit HIV-1 reverse transcription in non-cycling immune cells by limiting the supply of the dNTP substrates. Yet, phosphorylation of T592 downregulates SAMHD1 antiviral activity, but not its dNTPase function, implying that additional mechanisms contribute to viral restriction. Here, we show that SAMHD1 is SUMOylated on residue K595, a modification that relies on the presence of a proximal SUMO-interacting motif (SIM). Loss of K595 SUMOylation suppresses the restriction activity of SAMHD1, even in the context of the constitutively active phospho-ablative T592A mutant but has no impact on dNTP depletion. Conversely, the artificial fusion of SUMO2 to a non-SUMOylatable inactive SAMHD1 variant restores its antiviral function, a phenotype that is reversed by the phosphomimetic T
Identifiants
pubmed: 34321470
doi: 10.1038/s41467-021-24802-5
pii: 10.1038/s41467-021-24802-5
pmc: PMC8319325
doi:
Substances chimiques
SAM Domain and HD Domain-Containing Protein 1
EC 3.1.5.-
SAMHD1 protein, human
EC 3.1.5.-
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4582Subventions
Organisme : NIAID NIH HHS
ID : R01 AI150455
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI136581
Pays : United States
Organisme : NIGMS NIH HHS
ID : R25 GM086262
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150451
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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