Structural basis of MICAL autoinhibition.

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F24%3A00616793" target="_blank" >RIV/86652036:_____/24:00616793 - isvavai.cz</a>
Alternative codes found
RIV/68378050:_____/24:00616793 RIV/61388963:_____/24:00616793 RIV/00216208:11310/24:10489566 RIV/00216224:14740/24:00140048
Result on the web
<a href="https://www.nature.com/articles/s41467-024-54131-2" target="_blank" >https://www.nature.com/articles/s41467-024-54131-2</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-024-54131-2" target="_blank" >10.1038/s41467-024-54131-2</a>

Result language
angličtina
Original language name
Structural basis of MICAL autoinhibition.
Original language 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 3.1A. 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-L2alpha1-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.
Czech name
—
Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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