8Y6K

Cryo-EM structure of full-length MICAL1 in the autoinhibited state

8Y6K の概要

• エントリーDOI: 10.2210/pdb8y6k/pdb
• EMDBエントリー: 38989
• 分子名称: [F-actin]-monooxygenase MICAL1, ZINC ION, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: mical1, monooxygenase, f-actin disassembly, autoinhibition, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 118931.10

構造登録者

Niu, F.,Wei, Z. (登録日: 2024-02-02, 公開日: 2024-08-28, 最終更新日: 2024-09-25)

主引用文献

Lin, L.,Dong, J.,Xu, S.,Xiao, J.,Yu, C.,Niu, F.,Wei, Z.
Autoinhibition and relief mechanisms for MICAL monooxygenases in F-actin disassembly.
Nat Commun, 15:6824-6824, 2024

PubMed Abstract: MICAL proteins represent a unique family of actin regulators crucial for synapse development, membrane trafficking, and cytokinesis. Unlike classical actin regulators, MICALs catalyze the oxidation of specific residues within actin filaments to induce robust filament disassembly. The potent activity of MICALs requires tight control to prevent extensive damage to actin cytoskeleton. However, the molecular mechanism governing MICALs' activity regulation remains elusive. Here, we report the cryo-EM structure of MICAL1 in the autoinhibited state, unveiling a head-to-tail interaction that allosterically blocks enzymatic activity. The structure also reveals the assembly of C-terminal domains via a tripartite interdomain interaction, stabilizing the inhibitory conformation of the RBD. Our structural, biochemical, and cellular analyses elucidate a multi-step mechanism to relieve MICAL1 autoinhibition in response to the dual-binding of two Rab effectors, revealing its intricate activity regulation mechanisms. Furthermore, our mutagenesis study of MICAL3 suggests the conserved autoinhibition and relief mechanisms among MICALs.

PubMed: 39122694
DOI: 10.1038/s41467-024-50940-7

実験手法

ELECTRON MICROSCOPY (3.94 Å)