9LKX

local refinement of FEM1B bound with PLD6

9LKX の概要

• エントリーDOI: 10.2210/pdb9lkx/pdb
• EMDBエントリー: 63187
• 分子名称: Protein fem-1 homolog B, Mitochondrial cardiolipin hydrolase (2 entities in total)
• 機能のキーワード: ubiquitination e3 ligase, cryo-em, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93239.35

構造登録者

Zhao, S.,Xu, C. (登録日: 2025-01-16, 公開日: 2025-04-09, 最終更新日: 2025-05-07)

主引用文献

Raiff, A.,Zhao, S.,Bekturova, A.,Zenge, C.,Mazor, S.,Chen, X.,Ru, W.,Makaros, Y.,Ast, T.,Ordureau, A.,Xu, C.,Koren, I.
TOM20-driven E3 ligase recruitment regulates mitochondrial dynamics through PLD6.
Nat.Chem.Biol., 2025

PubMed Abstract: Mitochondrial homeostasis is maintained through complex regulatory mechanisms, including the balance of mitochondrial dynamics involving fusion and fission processes. A central player in this regulation is the ubiquitin-proteasome system (UPS), which controls the degradation of pivotal mitochondrial proteins. In this study, we identified cullin-RING E3 ligase 2 (CRL2) and its substrate receptor, FEM1B, as critical regulators of mitochondrial dynamics. Through proteomic analysis, we demonstrate here that FEM1B controls the turnover of PLD6, a key regulator of mitochondrial dynamics. Using structural and biochemical approaches, we show that FEM1B physically interacts with PLD6 and that this interaction is facilitated by the direct association of FEM1B with the mitochondrial import receptor TOM20. Ablation of FEM1B or disruption of the FEM1B-TOM20 interaction impairs PLD6 degradation and induces mitochondrial defects, phenocopying PLD6 overexpression. These findings underscore the importance of FEM1B in maintaining mitochondrial morphology and provide further mechanistic insights into how the UPS regulates mitochondrial homeostasis.

PubMed: 40263465
DOI: 10.1038/s41589-025-01894-4

実験手法

ELECTRON MICROSCOPY (3.76 Å)