PXD044767

PXD044767 is an original dataset announced via ProteomeXchange.

Title	How Myosin VI Traps its Off-State, is Activated and Dimerizes
Description	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, proper functioning of Myo6 relies on precise spatio-temporal 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.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_05:45:25.321.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tomos Morgan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-23 01:38:45	ID requested
⏵ 1	2024-01-26 05:45:27	announced

10.1038/s41467-023-42376-2;

Canon L, Kikuti C, Planelles-Herrero VJ, Lin T, Mayeux F, Sirkia H, Lee YI, Heidsieck L, Velikovsky L, David A, Liu X, Moussaoui D, Forest E, H, ö, ö, k P, Petersen KJ, Morgan TE, Di Cicco A, Sir, é, s-Campos J, Derivery E, L, é, vy D, Delevoye C, Sweeney HL, Houdusse A, How myosin VI traps its off-state, is activated and dimerizes. Nat Commun, 14(1):6732(2023) [pubmed]

submitter keyword: Myosin VI, Human, CLMS, cross linking mass spectromety

Anne Houdusse
contact affiliation	Structural Motility, UMR 144 CNRS/Curie Institute, PSL Research University, 26 rue d’Ulm, 75258 Paris cedex 05, France
contact email	anne.houdusse@curie.fr
lab head
Tomos Morgan
contact affiliation	MRC-LMB
contact email	tmorgan@mrc-lmb.cam.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD044767

PRIDE project URI

• PRIDE
  1. PXD044767
     1. Label: PRIDE project
     2. Name: How Myosin VI Traps its Off-State, is Activated and Dimerizes