9GR0
Interaction with AK2A links AIFM1 to cellular energy metabolism. The cryo-EM structure of dimeric AIFM1 bound by AK2A.
Summary for 9GR0
| Entry DOI | 10.2210/pdb9gr0/pdb |
| EMDB information | 51516 |
| Descriptor | Adenylate kinase 2, mitochondrial, Apoptosis-inducing factor 1, mitochondrial, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total) |
| Functional Keywords | complex, tetramer, nadh, fad, reduced, flavoprotein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 173737.24 |
| Authors | 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. (deposition date: 2024-09-10, release date: 2025-07-09) |
| Primary citation | 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, 2025 Cited by 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: 40578348DOI: 10.1016/j.molcel.2025.05.036 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.61 Å) |
Structure validation
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