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| | ==SOLUTION STRUCTURE OF APAF-1 CARD== | | ==SOLUTION STRUCTURE OF APAF-1 CARD== |
| - | <StructureSection load='1c15' size='340' side='right'caption='[[1c15]], [[NMR_Ensembles_of_Models | 16 NMR models]]' scene=''> | + | <StructureSection load='1c15' size='340' side='right'caption='[[1c15]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1c15]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C15 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1c15]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C15 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3crd|3crd]], [[1a1w|1a1w]], [[1ddf|1ddf]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1c15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c15 OCA], [https://pdbe.org/1c15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c15 RCSB], [https://www.ebi.ac.uk/pdbsum/1c15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c15 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=1c15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c15 OCA], [https://pdbe.org/1c15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c15 RCSB], [https://www.ebi.ac.uk/pdbsum/1c15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c15 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/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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chou, J]] | + | [[Category: Chou J]] |
| - | [[Category: Olea, R S]] | + | [[Category: Olea RS]] |
| - | [[Category: Wagner, G]] | + | [[Category: Wagner G]] |
| - | [[Category: Yuan, J]] | + | [[Category: Yuan J]] |
| - | [[Category: Zhou, P]] | + | [[Category: Zhou P]] |
| - | [[Category: Apaf]]
| + | |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Card]]
| + | |
| - | [[Category: Caspase recruitment domain]]
| + | |
| - | [[Category: Dd]]
| + | |
| - | [[Category: Ded]]
| + | |
| - | [[Category: Homophilic interaction]]
| + | |
| - | [[Category: Programmed cell death]]
| + | |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Direct recruitment and activation of caspase-9 by Apaf-1 through the homophilic CARD/CARD (Caspase Recruitment Domain) interaction is critical for the activation of caspases downstream of mitochondrial damage in apoptosis. Here we report the solution structure of the Apaf-1 CARD domain and its surface of interaction with caspase-9 CARD. Apaf-1 CARD consists of six tightly packed amphipathic alpha-helices and is topologically similar to the RAIDD CARD, with the exception of a kink observed in the middle of the N-terminal helix. By using chemical shift perturbation data, the homophilic interaction was mapped to the acidic surface of Apaf-1 CARD centered around helices 2 and 3. Interestingly, a significant portion of the chemically perturbed residues are hydrophobic, indicating that in addition to the electrostatic interactions predicted previously, hydrophobic interaction is also an important driving force underlying the CARD/CARD interaction. On the basis of the identified functional residues of Apaf-1 CARD and the surface charge complementarity, we propose a model of CARD/CARD interaction between Apaf-1 and caspase-9.
Solution structure of Apaf-1 CARD and its interaction with caspase-9 CARD: a structural basis for specific adaptor/caspase interaction.,Zhou P, Chou J, Olea RS, Yuan J, Wagner G Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11265-70. PMID:10500165[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
- ↑ Zhou P, Chou J, Olea RS, Yuan J, Wagner G. Solution structure of Apaf-1 CARD and its interaction with caspase-9 CARD: a structural basis for specific adaptor/caspase interaction. Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11265-70. PMID:10500165
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