5KVH
Crystal structure of human apoptosis-inducing factor with W196A mutation
Summary for 5KVH
| Entry DOI | 10.2210/pdb5kvh/pdb |
| Descriptor | Apoptosis-inducing factor 1, mitochondrial, FLAVIN-ADENINE DINUCLEOTIDE, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | oxidoreductase, flavoprotein, mitochondria, cell death |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 120374.06 |
| Authors | Brosey, C.A.,Nix, J.,Ellenberger, T.,Tainer, J.A. (deposition date: 2016-07-14, release date: 2016-11-16, Last modification date: 2023-10-04) |
| Primary citation | Brosey, C.A.,Ho, C.,Long, W.Z.,Singh, S.,Burnett, K.,Hura, G.L.,Nix, J.C.,Bowman, G.R.,Ellenberger, T.,Tainer, J.A. Defining NADH-Driven Allostery Regulating Apoptosis-Inducing Factor. Structure, 24:2067-2079, 2016 Cited by PubMed Abstract: Apoptosis-inducing factor (AIF) is critical for mitochondrial respiratory complex biogenesis and for mediating necroptotic parthanatos; these functions are seemingly regulated by enigmatic allosteric switching driven by NADH charge-transfer complex (CTC) formation. Here, we define molecular pathways linking AIF's active site to allosteric switching regions by characterizing dimer-permissive mutants using small-angle X-ray scattering (SAXS) and crystallography and by probing AIF-CTC communication networks using molecular dynamics simulations. Collective results identify two pathways propagating allostery from the CTC active site: (1) active-site H454 links to S480 of AIF's central β-strand to modulate a hydrophobic border at the dimerization interface, and (2) an interaction network links AIF's FAD cofactor, central β-strand, and Cβ-clasp whereby R529 reorientation initiates C-loop release during CTC formation. This knowledge of AIF allostery and its flavoswitch mechanism provides a foundation for biologically understanding and biomedically controlling its participation in mitochondrial homeostasis and cell death. PubMed: 27818101DOI: 10.1016/j.str.2016.09.012 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.273 Å) |
Structure validation
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