How myosin VI traps its off-state, is activated and dimerizes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 10 2023
23 10 2023
Historique:
received:
05
01
2023
accepted:
10
10
2023
medline:
27
10
2023
pubmed:
24
10
2023
entrez:
23
10
2023
Statut:
epublish
Résumé
Myosin VI (Myo6) is the only minus-end directed nanomotor on actin, allowing it to uniquely contribute to numerous cellular functions. As for other nanomotors, the proper functioning of Myo6 relies on precise spatiotemporal control of motor activity via a poorly defined off-state and interactions with partners. Our structural, functional, and cellular studies reveal key features of myosin regulation and indicate that not all partners can activate Myo6. TOM1 and Dab2 cannot bind the off-state, while GIPC1 binds Myo6, releases its auto-inhibition and triggers proximal dimerization. Myo6 partners thus differentially recruit Myo6. We solved a crystal structure of the proximal dimerization domain, and show that its disruption compromises endocytosis in HeLa cells, emphasizing the importance of Myo6 dimerization. Finally, we show that the L926Q deafness mutation disrupts Myo6 auto-inhibition and indirectly impairs proximal dimerization. Our study thus demonstrates the importance of partners in the control of Myo6 auto-inhibition, localization, and activation.
Identifiants
pubmed: 37872146
doi: 10.1038/s41467-023-42376-2
pii: 10.1038/s41467-023-42376-2
pmc: PMC10593786
doi:
Substances chimiques
myosin VI
0
Actins
0
Myosin Heavy Chains
EC 3.6.4.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6732Subventions
Organisme : Medical Research Council
ID : MC_UP_1201/13
Pays : United Kingdom
Organisme : NIDCD NIH HHS
ID : R01 DC009100
Pays : United States
Informations de copyright
© 2023. Springer Nature Limited.
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