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PXD057312

PXD057312 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructural basis of MICAL autoinhibition
DescriptionMICAL 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-30
AnnouncementXMLSubmission_2024-10-30_07:35:21.477.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPavla Vankova
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-10-29 13:53:35ID requested
12024-10-30 07:35:21announced
Publication List
Dataset with its publication pending
Keyword List
ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)
submitter keyword: F-actin depolymerization, actin, autoinhibition, Rab,MICAL
Contact List
Daniel Rozbesky
contact affiliationLaboratory of Structural Neurobiology, Institute of Molecular Genetics of the Czech Academy of Sciences - BioCeV,Prumyslova 595, 25250 Vestec, Czech Republic
contact emaildaniel.rozbesky@natur.cuni.cz
lab head
Pavla Vankova
contact affiliationInstitute of Biotechnology of the Czech Academy of Sciences, BioCeV, Prumyslova 595, 252 50 Vestec, Czech Republic
contact emailpavla.vankova@ibt.cas.cz
dataset submitter
Full Dataset Link List
Dataset FTP location
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