PXD057312

PXD057312 is an original dataset announced via ProteomeXchange.

Title	Structural basis of MICAL autoinhibition
Description	MICAL proteins play a crucial role in cellular dynamics by binding and disassembling actin filaments, impacting processes like axon guidance, cytokinesis, and cell morphology. Their cellular activity is tightly controlled, as dysregulation can lead to detrimental effects on cellular morphology. Although previous studies have suggested that MICALs are autoinhibited, and require Rab proteins to become active, the detailed molecular mechanisms remained unclear. Here, we report the cryo-EM structure of human MICAL1 at a nominal resolution of 3.1 Å. Structural analyses, alongside biochemical and functional studies, show that MICAL1 autoinhibition is mediated by an intramolecular interaction between its N-terminal catalytic and C-terminal coiled-coil domains, blocking F-actin interaction. Moreover, we demonstrate that allosteric changes in the coiled-coil domain and the binding of the tripartite assembly of CH-L2α1-LIM domains to the coiled-coil domain are crucial for MICAL activation and autoinhibition. These mechanisms appear to be evolutionarily conserved, suggesting a potential universality across the MICAL family.
HostingRepository	PRIDE
AnnounceDate	2024-10-30
AnnouncementXML	Submission_2024-10-30_07:35:21.477.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pavla Vankova
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-29 13:53:35	ID requested
⏵ 1	2024-10-30 07:35:21	announced

Dataset with its publication pending

ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)

submitter keyword: F-actin depolymerization, actin, autoinhibition, Rab,MICAL

Daniel Rozbesky
contact affiliation	Laboratory of Structural Neurobiology, Institute of Molecular Genetics of the Czech Academy of Sciences - BioCeV,Prumyslova 595, 25250 Vestec, Czech Republic
contact email	daniel.rozbesky@natur.cuni.cz
lab head
Pavla Vankova
contact affiliation	Institute of Biotechnology of the Czech Academy of Sciences, BioCeV, Prumyslova 595, 252 50 Vestec, Czech Republic
contact email	pavla.vankova@ibt.cas.cz
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/2024/10/PXD057312

PRIDE project URI

• PRIDE
  1. PXD057312
     1. Label: PRIDE project
     2. Name: Structural basis of MICAL autoinhibition