Structural basis of microtubule depolymerization by the kinesin-like activity of HIV-1 Rev.
CTT
HIV-1
Microtubules
Rev
Rings
Tubulin
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
05 10 2023
05 10 2023
Historique:
received:
17
08
2022
revised:
07
04
2023
accepted:
18
07
2023
pmc-release:
05
10
2024
medline:
9
10
2023
pubmed:
13
8
2023
entrez:
12
8
2023
Statut:
ppublish
Résumé
HIV-1 Rev is an essential regulatory protein that transports unspliced and partially spliced viral mRNAs from the nucleus to the cytoplasm for the expression of viral structural proteins. During its nucleocytoplasmic shuttling, Rev interacts with several host proteins to use the cellular machinery for the advantage of the virus. Here, we report the 3.5 Å cryo-EM structure of a 4.8 MDa Rev-tubulin ring complex. Our structure shows that Rev's arginine-rich motif (ARM) binds to both the acidic surfaces and the C-terminal tails of α/β-tubulin. The Rev-tubulin interaction is functionally homologous to that of kinesin-13, potently destabilizing microtubules at sub-stoichiometric levels. Expression of Rev in astrocytes and HeLa cells shows that it can modulate the microtubule cytoskeleton within the cellular environment. These results show a previously undefined regulatory role of Rev.
Identifiants
pubmed: 37572662
pii: S0969-2126(23)00251-4
doi: 10.1016/j.str.2023.07.009
pmc: PMC10592302
mid: NIHMS1920850
pii:
doi:
Substances chimiques
rev Gene Products, Human Immunodeficiency Virus
0
Kinesins
EC 3.6.4.4
Tubulin
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1233-1246.e5Subventions
Organisme : Intramural NIH HHS
ID : Z01 AR041115
Pays : United States
Informations de copyright
Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare that they have no conflicts of interest with the contents of this article.
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