4bur: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4bur]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BUR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BUR FirstGlance]. <br> | <table><tr><td colspan='2'>[[4bur]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BUR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BUR FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bv6|4bv6]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bv6|4bv6]]</td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bur FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bur OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bur RCSB], [http://www.ebi.ac.uk/pdbsum/4bur PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bur FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bur OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bur RCSB], [http://www.ebi.ac.uk/pdbsum/4bur PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Disease == | == Disease == | ||
[[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> | [[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> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Ferreira, P | [[Category: Ferreira, P]] | ||
[[Category: Herguedas, B | [[Category: Herguedas, B]] | ||
[[Category: Hermoso, J A | [[Category: Hermoso, J A]] | ||
[[Category: Martinez-Julvez, M | [[Category: Martinez-Julvez, M]] | ||
[[Category: Medina, M | [[Category: Medina, M]] | ||
[[Category: Villanueva, R | [[Category: Villanueva, R]] | ||
[[Category: Apoptosis]] | [[Category: Apoptosis]] | ||
[[Category: Dna-binding]] | [[Category: Dna-binding]] | ||
Revision as of 15:47, 5 January 2015
Crystal structure of the reduced human Apoptosis inducing factor complexed with NADCrystal structure of the reduced human Apoptosis inducing factor complexed with NAD
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] Publication Abstract from PubMedThe apoptosis-inducing factor (AIF) is a mitochondrial-flavoprotein that, after cell death induction, is distributed to the nucleus to mediate chromatinolysis. In mitochondria, AIF is present in a monomer-dimer equilibrium that after reduction by NADH gets displaced toward the dimer. The crystal structure of the human AIF (hAIF):NAD(H)-bound dimer revealed one FAD and, unexpectedly, two NAD(H) molecules per protomer. A 1:2 hAIF:NAD(H) binding stoichiometry was additionally confirmed in solution by using surface plasmon resonance. The here newly discovered NAD(H)-binding site includes residues mutated in human disorders, and accommodation of the coenzyme in it requires restructuring of a hAIF portion within the 509-560 apoptogenic segment. Disruption of interactions at the dimerization surface by production of the hAIF E413A/R422A/R430A mutant resulted in a nondimerizable variant considerably less efficiently stabilizing charge-transfer complexes upon coenzyme reduction than WT hAIF. These data reveal that the coenzyme-mediated monomer-dimer transition of hAIF modulates the conformation of its C-terminal proapoptotic domain, as well as its mechanism as reductase. These observations suggest that both the mitochondrial and apoptotic functions of hAIF are interconnected and coenzyme controlled: a key information in the understanding of the physiological role of AIF in the cellular life and death cycle. Structural insights into the coenzyme mediated monomer-dimer transition of the pro-apoptotic apoptosis inducing factor.,Ferreira P, Villanueva R, Martinez-Julvez M, Herguedas B, Marcuello C, Fernandez-Silva P, Cabon L, Hermoso JA, Lostao A, Susin SA, Medina M Biochemistry. 2014 Jul 1;53(25):4204-15. doi: 10.1021/bi500343r. Epub 2014 Jun, 20. PMID:24914854[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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