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| | <SX load='3j2t' size='340' side='right' viewer='molstar' caption='[[3j2t]], [[Resolution|resolution]] 9.50Å' scene=''> | | <SX load='3j2t' size='340' side='right' viewer='molstar' caption='[[3j2t]], [[Resolution|resolution]] 9.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3j2t]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3iza 3iza] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3iyt 3iyt]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J2T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3J2T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3j2t]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3iza 3iza] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3iyt 3iyt]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J2T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3J2T FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 9.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Apaf-1, APAF1, KIAA0413 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=3j2t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j2t OCA], [https://pdbe.org/3j2t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3j2t RCSB], [https://www.ebi.ac.uk/pdbsum/3j2t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3j2t ProSAT]</span></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=3j2t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j2t OCA], [https://pdbe.org/3j2t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3j2t RCSB], [https://www.ebi.ac.uk/pdbsum/3j2t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3j2t ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/APAF_HUMAN APAF_HUMAN]] Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis.<ref>PMID:10393175</ref> <ref>PMID:12804598</ref> [[https://www.uniprot.org/uniprot/CYC_BOVIN CYC_BOVIN]] Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain. Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases (By similarity).
| + | [https://www.uniprot.org/uniprot/APAF_HUMAN APAF_HUMAN] Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis.<ref>PMID:10393175</ref> <ref>PMID:12804598</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </SX> | | </SX> |
| | [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Akey, C W]] | + | [[Category: Akey CW]] |
| - | [[Category: Topf, M]] | + | [[Category: Topf M]] |
| - | [[Category: Yuan, S]] | + | [[Category: Yuan S]] |
| - | [[Category: Apaf-1]]
| + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Apoptosis protease activating factor-1]]
| + | |
| - | [[Category: Cytochrome c]]
| + | |
| Structural highlights
Function
APAF_HUMAN Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis.[1] [2]
Publication Abstract from PubMed
Apoptosome assembly is highly regulated in the intrinsic cell death pathway. To better understand this step, we created an improved model of the human apoptosome using a crystal structure of full length Apaf-1 and a single particle, electron density map at approximately 9.5 A resolution. The apoptosome model includes N-terminal domains of Apaf-1, cognate beta-propellers, and cytochrome c. A direct comparison of Apaf-1 in the apoptosome and as a monomer reveals conformational changes that occur during the first two steps of assembly. This includes an induced-fit mechanism for cytochrome c binding to regulatory beta-propellers, which is dependent on shape and charge complementarity, and a large rotation of the nucleotide binding module during nucleotide exchange. These linked conformational changes create an extended Apaf-1 monomer and drive apoptosome assembly. Moreover, the N-terminal CARD in the inactive Apaf-1 monomer is not shielded from other proteins by beta-propellers. Hence, the Apaf-1 CARD may be free to interact with a procaspase-9 CARD either before or during apoptosome assembly. Irrespective of the timing, the end product of assembly is a holo-apoptosome with an acentric CARD-CARD disk and tethered pc-9 catalytic domains. Subsequent activation of pc-9 leads to a proteolytic cascade and cell death.
Changes in apaf-1 conformation that drive apoptosome assembly.,Yuan S, Topf M, Reubold TF, Eschenburg S, Akey CW Biochemistry. 2013 Apr 2;52(13):2319-27. doi: 10.1021/bi301721g. Epub 2013 Mar, 22. PMID:23521171[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hu Y, Benedict MA, Ding L, Nunez G. Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis. EMBO J. 1999 Jul 1;18(13):3586-95. PMID:10393175 doi:10.1093/emboj/18.13.3586
- ↑ Ogawa T, Shiga K, Hashimoto S, Kobayashi T, Horii A, Furukawa T. APAF-1-ALT, a novel alternative splicing form of APAF-1, potentially causes impeded ability of undergoing DNA damage-induced apoptosis in the LNCaP human prostate cancer cell line. Biochem Biophys Res Commun. 2003 Jun 27;306(2):537-43. PMID:12804598
- ↑ Yuan S, Topf M, Reubold TF, Eschenburg S, Akey CW. Changes in apaf-1 conformation that drive apoptosome assembly. Biochemistry. 2013 Apr 2;52(13):2319-27. doi: 10.1021/bi301721g. Epub 2013 Mar, 22. PMID:23521171 doi:http://dx.doi.org/10.1021/bi301721g
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