9EII

Import stalled PINK1 TOM complex, symmetry expanded

Summary for 9EII

• Entry DOI: 10.2210/pdb9eii/pdb
• EMDB information: 48084
• Descriptor: Serine/threonine-protein kinase PINK1, mitochondrial, Mitochondrial import receptor subunit TOM20 homolog, Voltage-dependent anion-selective channel protein 2, ... (9 entities in total)
• Functional Keywords: pink1, tom complex, vdac, translocase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 13
• Total formula weight: 268131.64

Authors

Kirk, N.S.,Glukhova, A.,Callegari, S.,Komander, D. (deposition date: 2024-11-26, release date: 2025-03-12, Last modification date: 2025-03-26)

Primary citation

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, :eadu6445-eadu6445, 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-Å resolution cryo-electron microscopy structure of dimeric human PINK1 stabilized at an endogenous array of mitochondrial TOM and 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

Experimental method

ELECTRON MICROSCOPY (2.75 Å)