9GR0

Interaction with AK2A links AIFM1 to cellular energy metabolism. The cryo-EM structure of dimeric AIFM1 bound by AK2A.

9GR0 の概要

• エントリーDOI: 10.2210/pdb9gr0/pdb
• EMDBエントリー: 51516
• 分子名称: Adenylate kinase 2, mitochondrial, Apoptosis-inducing factor 1, mitochondrial, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: complex, tetramer, nadh, fad, reduced, flavoprotein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 173737.24

構造登録者

Rothemann, R.A.,Pavlenko, E.A.,Gerlich, S.,Grobushkin, P.,Mostert, S.,Stobbe, D.,Racho, J.,Stillger, K.,Lapacz, K.,Petrungaro, C.,Dengjel, J.,Neundorf, I.,Bano, D.,Mondal, M.,Weiss, K.,Ehninger, D.,Nguyen, T.H.D.,Poepsel, S.P.,Riemer, J. (登録日: 2024-09-10, 公開日: 2025-07-09, 最終更新日: 2025-07-16)

主引用文献

Rothemann, R.A.,Pavlenko, E.,Mondal, M.,Gerlich, S.,Grobushkin, P.,Mostert, S.,Racho, J.,Weiss, K.,Stobbe, D.,Stillger, K.,Lapacz, K.,Salscheider, S.L.,Petrungaro, C.,Ehninger, D.,Nguyen, T.H.D.,Dengjel, J.,Neundorf, I.,Bano, D.,Poepsel, S.,Riemer, J.
Interaction with AK2A links AIFM1 to cellular energy metabolism.
Mol.Cell, 85:2550-, 2025

PubMed Abstract: Apoptosis-inducing factor 1 (AIFM1) is a flavoprotein essential for mitochondrial function and biogenesis. Its interaction with MIA40/CHCHD4, the central component of the mitochondrial disulfide relay, accounts for some, but not all, aspects of AIFM1 function. We provide a high-confidence AIFM1 interactome that elucidates functional partners within the mitochondrial intermembrane space. We found that AIFM1 binding to adenylate kinase 2 (AK2), an essential enzyme that maintains cellular adenine nucleotide pools, depends on the AK2 C-terminal domain. High-resolution cryoelectron microscopy (cryo-EM) and biochemical analyses showed that both MIA40 and AK2A bind the AIFM1 C-terminal β-sheet domain. Their binding enhances NADH oxidoreductase activity by locking an active dimer conformation and, in the case of MIA40, affecting the cofactor-binding site. The AIFM1-AK2A interaction is important during mitochondrial respiration because AIFM1 serves as a recruiting hub within the IMS, regulating mitochondrial bioenergetic output by creating hotspots of metabolic enzymes.

PubMed: 40578348
DOI: 10.1016/j.molcel.2025.05.036

実験手法

ELECTRON MICROSCOPY (2.61 Å)