1m6i: Difference between revisions

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-[[Image:1m6i.gif|left|200px]]
- {{Structure
+==Crystal Structure of Apoptosis Inducing Factor (AIF)==
-|PDB= 1m6i |SIZE=350|CAPTION= <scene name='initialview01'>1m6i</scene>, resolution 1.8&Aring;
+<StructureSection load='1m6i' size='340' side='right'caption='[[1m6i]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE DINUCLEOTIDE'>FAD</scene>
+<table><tr><td colspan='2'>[[1m6i]] 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=1M6I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M6I FirstGlance]. <br>
-|ACTIVITY=
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
-|GENE=
+<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></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=1m6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m6i OCA], [https://pdbe.org/1m6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m6i RCSB], [https://www.ebi.ac.uk/pdbsum/1m6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m6i 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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m6/1m6i_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1m6i ConSurf].
+<div style="clear:both"></div>
-'''Crystal Structure of Apoptosis Inducing Factor (AIF)'''
+==See Also==
+*[[Cell death protein 3D structures|Cell death protein 3D structures]]
+== References ==
-==Overview==
+<references/>
-The execution of apoptosis or programmed cell death comprises both caspase-dependent and caspase-independent processes. Apoptosis inducing factor (AIF) was identified as a major player in caspase-independent cell death. It induces chromatin condensation and initial DNA cleavage via an unknown molecular mechanism. Here we report the crystal structure of human AIF at 1.8 A resolution. The structure reveals the presence of a strong positive electrostatic potential at the AIF surface, although the calculated isoelectric point for the entire protein is neutral. We show that recombinant AIF interacts with DNA in a sequence-independent manner. In addition, in cells treated with an apoptotic stimulus, endogenous AIF becomes co-localized with DNA at an early stage of nuclear morphological changes. Structure-based mutagenesis shows that DNA-binding defective mutants of AIF fail to induce cell death while retaining nuclear translocation. The potential DNA-binding site identified from mutagenesis also coincides with computational docking of a DNA duplex. These observations suggest that AIF-induced nuclear apoptosis requires a direct interaction with DNA.
+__TOC__
+</StructureSection>
-==About this Structure==
-M6I is a [[Single protein]] structure of 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=1M6I OCA].
-==Reference==
-DNA binding is required for the apoptogenic action of apoptosis inducing factor., Ye H, Cande C, Stephanou NC, Jiang S, Gurbuxani S, Larochette N, Daugas E, Garrido C, Kroemer G, Wu H, Nat Struct Biol. 2002 Sep;9(9):680-4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12198487 12198487]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Cande, C.]]
+[[Category: Cande C]]
-[[Category: Daugas, E.]]
+[[Category: Daugas E]]
-[[Category: Garrido, C.]]
+[[Category: Garrido C]]
-[[Category: Gurbuxani, S.]]
+[[Category: Gurbuxani S]]
-[[Category: Jiang, S.]]
+[[Category: Jiang S]]
-[[Category: Kroemer, G.]]
+[[Category: Kroemer G]]
-[[Category: Larochette, N.]]
+[[Category: Larochette N]]
-[[Category: Stephanou, N C.]]
+[[Category: Stephanou NC]]
-[[Category: Wu, H.]]
+[[Category: Wu H]]
-[[Category: Ye, H.]]
+[[Category: Ye H]]
-[[Category: FAD]]
-[[Category: aif]]
-[[Category: apoptosis]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:39:33 2008''