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5kvh
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human apoptosis-inducing factor with W196A mutation== | |
| + | <StructureSection load='5kvh' size='340' side='right'caption='[[5kvh]], [[Resolution|resolution]] 2.27Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5kvh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KVH FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.273Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5kvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kvh OCA], [https://pdbe.org/5kvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kvh RCSB], [https://www.ebi.ac.uk/pdbsum/5kvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kvh ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/AIFM1_HUMAN AIFM1_HUMAN] Defects in AIFM1 are the cause of combined oxidative phosphorylation deficiency type 6 (COXPD6) [MIM:[https://omim.org/entry/300816 300816]. It is a mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting.<ref>PMID:20362274</ref> <ref>PMID:22019070</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/AIFM1_HUMAN AIFM1_HUMAN] Probable oxidoreductase that has a dual role in controlling cellular life and death; during apoptosis, it is translocated from the mitochondria to the nucleus to function as a proapoptotic factor in a caspase-independent pathway, while in normal mitochondria, it functions as an antiapoptotic factor via its oxidoreductase activity. The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA. Interacts with EIF3G,and thereby inhibits the EIF3 machinery and protein synthesis, and activates casapse-7 to amplify apoptosis. Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells. Binds to DNA in a sequence-independent manner.<ref>PMID:17094969</ref> <ref>PMID:19418225</ref> <ref>PMID:20362274</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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 beta-strand to modulate a hydrophobic border at the dimerization interface, and (2) an interaction network links AIF's FAD cofactor, central beta-strand, and Cbeta-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. | ||
| - | + | Defining NADH-Driven Allostery Regulating Apoptosis-Inducing Factor.,Brosey CA, Ho C, Long WZ, Singh S, Burnett K, Hura GL, Nix JC, Bowman GR, Ellenberger T, Tainer JA Structure. 2016 Dec 6;24(12):2067-2079. doi: 10.1016/j.str.2016.09.012. Epub 2016, Nov 3. PMID:27818101<ref>PMID:27818101</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5kvh" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Cell death protein 3D structures|Cell death protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Brosey CA]] | ||
| + | [[Category: Ellenberger T]] | ||
| + | [[Category: Nix J]] | ||
| + | [[Category: Tainer JA]] | ||
Current revision
Crystal structure of human apoptosis-inducing factor with W196A mutation
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