9EII

Import stalled PINK1 TOM complex, symmetry expanded

9EII の概要

• エントリーDOI: 10.2210/pdb9eii/pdb
• EMDBエントリー: 48084
• 分子名称: Serine/threonine-protein kinase PINK1, mitochondrial, Mitochondrial import receptor subunit TOM20 homolog, Voltage-dependent anion-selective channel protein 2, ... (9 entities in total)
• 機能のキーワード: pink1, tom complex, vdac, translocase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 13
• 化学式量合計: 268131.64

構造登録者

Kirk, N.S.,Glukhova, A.,Callegari, S.,Komander, D. (登録日: 2024-11-26, 公開日: 2025-03-12, 最終更新日: 2025-04-30)

主引用文献

Callegari, S.,Kirk, N.S.,Gan, Z.Y.,Dite, T.,Cobbold, S.A.,Leis, A.,Dagley, L.F.,Glukhova, A.,Komander, D.
Structure of human PINK1 at a mitochondrial TOM-VDAC array.
Science, 388:303-310, 2025

PubMed Abstract: Mutations in the ubiquitin kinase PINK1 cause early-onset Parkinson's disease, but how PINK1 is stabilized at depolarized mitochondrial translocase complexes has remained poorly understood. We determined a 3.1-angstrom resolution cryo-electron microscopy structure of dimeric human PINK1 stabilized at an endogenous array of mitochondrial translocase of the outer membrane (TOM) and voltage-dependent anion channel (VDAC) complexes. Symmetric arrangement of two TOM core complexes around a central VDAC2 dimer is facilitated by TOM5 and TOM20, both of which also bind PINK1 kinase C-lobes. PINK1 enters mitochondria through the proximal TOM40 barrel of the TOM core complex, guided by TOM7 and TOM22. Our structure explains how human PINK1 is stabilized at the TOM complex and regulated by oxidation, uncovers a previously unknown TOM-VDAC assembly, and reveals how a physiological substrate traverses TOM40 during translocation.

PubMed: 40080546
DOI: 10.1126/science.adu6445

実験手法

ELECTRON MICROSCOPY (2.75 Å)