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| - | {{STRUCTURE_4lii| PDB=4lii | SCENE= }} | |
| - | ===Crystal structure of an apoptosis-inducing factor, mitochondrion-associated, 1 (AIFM1) from Homo sapiens at 1.88 A resolution=== | |
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| - | ==Disease== | + | ==Crystal structure of an apoptosis-inducing factor, mitochondrion-associated, 1 (AIFM1) from Homo sapiens at 1.88 A resolution== |
| - | [[http://www.uniprot.org/uniprot/AIFM1_HUMAN AIFM1_HUMAN]] Defects in AIFM1 are the cause of combined oxidative phosphorylation deficiency type 6 (COXPD6) [MIM:[http://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> | + | <StructureSection load='4lii' size='340' side='right'caption='[[4lii]], [[Resolution|resolution]] 1.88Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[4lii]] is a 1 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=4LII OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LII FirstGlance]. <br> |
| | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4lii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lii OCA], [https://pdbe.org/4lii PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lii RCSB], [https://www.ebi.ac.uk/pdbsum/4lii PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lii 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> |
| | | | |
| - | ==Function== | + | ==See Also== |
| - | [[http://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> | + | *[[Cell death protein 3D structures|Cell death protein 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure==
| + | <references/> |
| - | [[4lii]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LII OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference== | + | |
| - | <references group="xtra"/><references/> | + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: JCSG, Joint Center for Structural Genomics.]] | + | [[Category: Large Structures]] |
| - | [[Category: TCELL, Partnership for T-Cell Biology.]]
| + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Fad/nad-linked reductase]]
| + | |
| - | [[Category: Flavoprotein]]
| + | |
| - | [[Category: Jcsg]]
| + | |
| - | [[Category: Joint center for structural genomic]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Protein structure initiative]]
| + | |
| - | [[Category: Psi-biology]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| Structural highlights
Disease
AIFM1_HUMAN Defects in AIFM1 are the cause of combined oxidative phosphorylation deficiency type 6 (COXPD6) [MIM:300816. It is a mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting.[1] [2]
Function
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.[3] [4] [5]
See Also
References
- ↑ Ghezzi D, Sevrioukova I, Invernizzi F, Lamperti C, Mora M, D'Adamo P, Novara F, Zuffardi O, Uziel G, Zeviani M. Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor. Am J Hum Genet. 2010 Apr 9;86(4):639-49. doi: 10.1016/j.ajhg.2010.03.002. Epub, 2010 Apr 1. PMID:20362274 doi:10.1016/j.ajhg.2010.03.002
- ↑ Berger I, Ben-Neriah Z, Dor-Wolman T, Shaag A, Saada A, Zenvirt S, Raas-Rothschild A, Nadjari M, Kaestner KH, Elpeleg O. Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing. Mol Genet Metab. 2011 Dec;104(4):517-20. doi: 10.1016/j.ymgme.2011.09.020. Epub, 2011 Sep 24. PMID:22019070 doi:10.1016/j.ymgme.2011.09.020
- ↑ Kim JT, Kim KD, Song EY, Lee HG, Kim JW, Kim JW, Chae SK, Kim E, Lee MS, Yang Y, Lim JS. Apoptosis-inducing factor (AIF) inhibits protein synthesis by interacting with the eukaryotic translation initiation factor 3 subunit p44 (eIF3g). FEBS Lett. 2006 Nov 27;580(27):6375-83. Epub 2006 Nov 3. PMID:17094969 doi:10.1016/j.febslet.2006.10.049
- ↑ Son YO, Jang YS, Heo JS, Chung WT, Choi KC, Lee JC. Apoptosis-inducing factor plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells. Apoptosis. 2009 Jun;14(6):796-808. doi: 10.1007/s10495-009-0353-7. PMID:19418225 doi:10.1007/s10495-009-0353-7
- ↑ Ghezzi D, Sevrioukova I, Invernizzi F, Lamperti C, Mora M, D'Adamo P, Novara F, Zuffardi O, Uziel G, Zeviani M. Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor. Am J Hum Genet. 2010 Apr 9;86(4):639-49. doi: 10.1016/j.ajhg.2010.03.002. Epub, 2010 Apr 1. PMID:20362274 doi:10.1016/j.ajhg.2010.03.002
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