Structural basis of MICAL autoinhibition

J 2024

Structural basis of MICAL autoinhibition

HORVATH, Matej; Adam SCHROFEL; Karolina KOWALSKA; Jan SABO; Jonas VLASAK et. al.

Základní údaje

Originální název

Structural basis of MICAL autoinhibition

Autoři

HORVATH, Matej; Adam SCHROFEL; Karolina KOWALSKA; Jan SABO; Jonas VLASAK; Farahdokht NOURISANAMI; Margarita SOBOL; Daniel PINKAS (203 Česká republika, domácí); Krystof KNAPP; Nicola KOUPILOVA; Jiří NOVÁČEK (203 Česká republika, domácí); Vaclav VEVERKA; Zdenek LANSKY a Daniel ROZBESKY

Vydání

Nature Communications, Berlin, Nature Research, 2024, 2041-1723

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 14.700 v roce 2023

Kód RIV

RIV/00216224:14740/24:00140048

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1038/s41467-024-54131-2

UT WoS

001354231300034

EID Scopus

2-s2.0-85209172559

Klíčová slova anglicky

F-ACTIN; MONOOXYGENASE; VISUALIZATION; DYNAMICS; MOLECULE; DOMAIN; STATES; TOOLS; CASL; LOOP

Štítky

CF CRYO, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 7. 5. 2025 14:12, Mgr. Eva Dubská

Anotace

V originále

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 & Aring;. 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-L2 alpha 1-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.

Návaznosti

EF18_046/0015974, projekt VaV

Název: Modernizace České infrastruktury pro integrativní strukturní biologii

90242, velká výzkumná infrastruktura

Název: CIISB III

90250, velká výzkumná infrastruktura

Název: Czech-BioImaging III

Citovat

HORVATH, Matej; Adam SCHROFEL; Karolina KOWALSKA; Jan SABO; Jonas VLASAK; Farahdokht NOURISANAMI; Margarita SOBOL; Daniel PINKAS; Krystof KNAPP; Nicola KOUPILOVA; Jiří NOVÁČEK; Vaclav VEVERKA; Zdenek LANSKY a Daniel ROZBESKY. Structural basis of MICAL autoinhibition. Nature Communications. Berlin: Nature Research, 2024, roč. 15, č. 1, s. 1-13. ISSN 2041-1723. Dostupné z: https://dx.doi.org/10.1038/s41467-024-54131-2.

@article{2495357,
   author = {Horvath, Matej and Schrofel, Adam and Kowalska, Karolina and Sabo, Jan and Vlasak, Jonas and Nourisanami, Farahdokht and Sobol, Margarita and Pinkas, Daniel and Knapp, Krystof and Koupilova, Nicola and Nováček, Jiří and Veverka, Vaclav and Lansky, Zdenek and Rozbesky, Daniel},
   article_location = {Berlin},
   article_number = {1},
   doi = {http://dx.doi.org/10.1038/s41467-024-54131-2},
   keywords = {F-ACTIN; MONOOXYGENASE; VISUALIZATION; DYNAMICS; MOLECULE; DOMAIN; STATES; TOOLS; CASL; LOOP},
   language = {eng},
   issn = {2041-1723},
   journal = {Nature Communications},
   title = {Structural basis of MICAL autoinhibition},
   url = {https://www.nature.com/articles/s41467-024-54131-2},
   volume = {15},
   year = {2024}
}

TY  - JOUR
ID  - 2495357
AU  - Horvath, Matej - Schrofel, Adam - Kowalska, Karolina - Sabo, Jan - Vlasak, Jonas - Nourisanami, Farahdokht - Sobol, Margarita - Pinkas, Daniel - Knapp, Krystof - Koupilova, Nicola - Nováček, Jiří - Veverka, Vaclav - Lansky, Zdenek - Rozbesky, Daniel
PY  - 2024
TI  - Structural basis of MICAL autoinhibition
JF  - Nature Communications
VL  - 15
IS  - 1
SP  - 1-13
EP  - 1-13
PB  - Nature Research
SN  - 20411723
KW  - F-ACTIN
KW  - MONOOXYGENASE
KW  - VISUALIZATION
KW  - DYNAMICS
KW  - MOLECULE
KW  - DOMAIN
KW  - STATES
KW  - TOOLS
KW  - CASL
KW  - LOOP
UR  - https://www.nature.com/articles/s41467-024-54131-2
N2  - 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 & Aring;. 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-L2 alpha 1-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.
ER  -

HORVATH, Matej; Adam SCHROFEL; Karolina KOWALSKA; Jan SABO; Jonas VLASAK; Farahdokht NOURISANAMI; Margarita SOBOL; Daniel PINKAS; Krystof KNAPP; Nicola KOUPILOVA; Jiří NOVÁČEK; Vaclav VEVERKA; Zdenek LANSKY a Daniel ROZBESKY. Structural basis of MICAL autoinhibition. \textit{Nature Communications}. Berlin: Nature Research, 2024, roč.~15, č.~1, s.~1-13. ISSN~2041-1723. Dostupné z: https://dx.doi.org/10.1038/s41467-024-54131-2.

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