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New page: left|200px<br /> <applet load="1c15" size="450" color="white" frame="true" align="right" spinBox="true" caption="1c15" /> '''SOLUTION STRUCTURE OF APAF-1 CARD'''<br /> ...
 
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[[Image:1c15.gif|left|200px]]<br />
<applet load="1c15" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1c15" />
'''SOLUTION STRUCTURE OF APAF-1 CARD'''<br />


==Overview==
==SOLUTION STRUCTURE OF APAF-1 CARD==
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.
<StructureSection load='1c15' size='340' side='right'caption='[[1c15]]' scene=''>
== Structural highlights ==
<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='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>
</table>
== 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>
== 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/c1/1c15_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=1c15 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


==About this Structure==
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<ref>PMID:10500165</ref>
1C15 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1C15 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10500165 10500165]
</div>
<div class="pdbe-citations 1c15" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Apoptotic protease-activating factor-1 3D structures|Apoptotic protease-activating factor-1 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[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: card]]
[[Category: caspase recruitment domain]]
[[Category: dd]]
[[Category: ded]]
[[Category: homophilic interaction]]
[[Category: programmed cell death]]
 
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