{"database":"bioimages","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":[null],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-BIAD1515"],"repository":["bioimages"],"figure_sub":["Specimen","Image analysis","Annotations","Funding","Study Component","organisation","Biosample","Image correlation","Associations","Image acquisition"],"pubmed_authors":["Chris Brosey","John Tainer"],"additional_accession":[]},"is_claimable":false,"name":"NADH-bound AIF activates the mitochondrial CHCHD4/MIA40 chaperone by a substrate-mimicry mechanism","description":"Mitochondrial metabolism requires chaperoned import of disulfide-stabilized proteins via CHCHD4/MIA40 and its enigmatic interaction with oxidoreductase Apoptosis-Inducing Factor (AIF). By crystallizing human CHCHD4’s AIF-interaction domain with an activated AIF dimer, we uncover how NADH allosterically configures AIF to anchor CHCHD4’s β-hairpin and histidine helix motifs  to the inner mitochondrial membrane. The structure further reveals similarity between the AIF-interaction domain and recognition sequences of CHCHD4 substrates. NMR and X-ray scattering (SAXS) solution measurements, mutational analyses, and biochemistry show that the substrate-mimicking AIF-interaction domain shields CHCHD4’s redox-sensitive active site. Disrupting this shield critically activates CHCHD4 substrate affini","dates":{"release":"2024-12-31T00:00:00Z","modification":"2024-12-31T18:26:26.016Z","creation":"2024-12-11T00:46:57.483Z"},"accession":"S-BIAD1515","cross_references":{}}