[English] 日本語
Yorodumi
- PDB-9gqy: Interaction with AK2A links AIFM1 to cellular energy metabolism. ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9gqy
TitleInteraction with AK2A links AIFM1 to cellular energy metabolism. The cryo-EM structure of dimeric AIFM1 without any binding partner.
ComponentsApoptosis-inducing factor 1, mitochondrial
KeywordsFLAVOPROTEIN / Complex / Homodimer / NADH / FAD / Reduced
Function / homology
Function and homology information


Oxidoreductases; Acting on NADH or NADPH; With unknown physiological acceptors / mitochondrial disulfide relay system / cellular response to aldosterone / mitochondrial respiratory chain complex assembly / protein import into mitochondrial intermembrane space / poly-ADP-D-ribose binding / NAD(P)H oxidase H2O2-forming activity / positive regulation of necroptotic process / response to L-glutamate / oxidoreductase activity, acting on NAD(P)H ...Oxidoreductases; Acting on NADH or NADPH; With unknown physiological acceptors / mitochondrial disulfide relay system / cellular response to aldosterone / mitochondrial respiratory chain complex assembly / protein import into mitochondrial intermembrane space / poly-ADP-D-ribose binding / NAD(P)H oxidase H2O2-forming activity / positive regulation of necroptotic process / response to L-glutamate / oxidoreductase activity, acting on NAD(P)H / NADH dehydrogenase activity / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / FAD binding / cellular response to nitric oxide / response to ischemia / cellular response to estradiol stimulus / mitochondrial intermembrane space / response to toxic substance / cellular response to hydrogen peroxide / neuron differentiation / positive regulation of neuron apoptotic process / cellular response to hypoxia / mitochondrial inner membrane / protein dimerization activity / positive regulation of apoptotic process / apoptotic process / perinuclear region of cytoplasm / mitochondrion / DNA binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Mitochondrial apoptosis-inducing factor, C-terminal domain / Apoptosis-inducing factor, mitochondrion-associated, C-term / Apoptosis-inducing factor, mitochondrion-associated, C-term / : / FAD/NAD-linked reductase, dimerisation domain superfamily / FAD/NAD(P)-binding domain / Pyridine nucleotide-disulphide oxidoreductase / FAD/NAD(P)-binding domain superfamily
Similarity search - Domain/homology
FLAVIN-ADENINE DINUCLEOTIDE / NICOTINAMIDE-ADENINE-DINUCLEOTIDE / Apoptosis-inducing factor 1, mitochondrial
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å
AuthorsRothemann, R.A. / Pavlenko, E.A. / Gerlich, S. / Grobushkin, P. / Mostert, S. / Stobbe, D. / Racho, J. / Stillger, K. / Lapacz, K. / Petrungaro, C. ...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.
Funding support Germany, 4items
OrganizationGrant numberCountry
German Research Foundation (DFG)RI2150/5-1 Germany
German Research Foundation (DFG)SPP2453 Germany
German Research Foundation (DFG)RTG2550/1 Germany
German Research Foundation (DFG)455 SFB1430 Germany
CitationJournal: Mol Cell / Year: 2025
Title: Interaction with AK2A links AIFM1 to cellular energy metabolism.
Authors: Robin Alexander Rothemann / Egor Pavlenko / Mrityunjoy Mondal / Sarah Gerlich / Pavel Grobushkin / Sebastian Mostert / Julia Racho / Konstantin Weiss / Dylan Stobbe / Katharina Stillger / ...Authors: Robin Alexander Rothemann / Egor Pavlenko / Mrityunjoy Mondal / Sarah Gerlich / Pavel Grobushkin / Sebastian Mostert / Julia Racho / Konstantin Weiss / Dylan Stobbe / Katharina Stillger / Kim Lapacz / Silja Lucia Salscheider / Carmelina Petrungaro / Dan Ehninger / Thi Hoang Duong Nguyen / Jörn Dengjel / Ines Neundorf / Daniele Bano / Simon Poepsel / Jan Riemer /
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 ...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.
History
DepositionSep 10, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 9, 2025Provider: repository / Type: Initial release
Revision 1.1Jul 16, 2025Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.journal_volume / _citation.page_first / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
B: Apoptosis-inducing factor 1, mitochondrial
C: Apoptosis-inducing factor 1, mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)120,7046
Polymers117,8062
Non-polymers2,8984
Water18010
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein Apoptosis-inducing factor 1, mitochondrial / Programmed cell death protein 8


Mass: 58902.832 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: AIFM1, AIF, PDCD8 / Production host: Escherichia coli (E. coli) / Strain (production host): ROSETTA 2
References: UniProt: O95831, Oxidoreductases; Acting on NADH or NADPH; With unknown physiological acceptors
#2: Chemical ChemComp-FAD / FLAVIN-ADENINE DINUCLEOTIDE


Mass: 785.550 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H33N9O15P2 / Feature type: SUBJECT OF INVESTIGATION / Comment: FAD*YM
#3: Chemical ChemComp-NAD / NICOTINAMIDE-ADENINE-DINUCLEOTIDE


Mass: 663.425 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C21H27N7O14P2 / Comment: NAD*YM
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 10 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Dimeric Complex of Apoptosis inducing factor mitochondrial 1 (AIFM1)
Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.2 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli (E. coli) / Strain: ROSETTA 2 / Plasmid: pET-24a(+)
Buffer solutionpH: 7.4
Buffer component
IDConc.NameFormulaBuffer-ID
10.1 mMNicotinamide adenine dinucleotideNADH1
2100 mMSodium ChlorideNaCl1
320 mMTris(hydroxymethyl)aminomethanTris/Cl1
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN
Electron lensMode: OTHER / Nominal defocus max: 1700 nm / Nominal defocus min: 700 nm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON IV (4k x 4k)
EM imaging opticsEnergyfilter name: TFS Selectris

-
Processing

EM software
IDNameVersionCategory
1Topazparticle selection
2PHENIX1.21_5207:model refinement
3cryoSPARCimage acquisition
4cryoSPARCmasking
5cryoSPARCCTF correction
6Cootmodel fitting
12cryoSPARCclassification
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 225612 / Symmetry type: POINT
Atomic model buildingProtocol: AB INITIO MODEL / Space: REAL
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0047201
ELECTRON MICROSCOPYf_angle_d0.5589767
ELECTRON MICROSCOPYf_dihedral_angle_d7.3981161
ELECTRON MICROSCOPYf_chiral_restr0.0461075
ELECTRON MICROSCOPYf_plane_restr0.0051234

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more