3ygs: Difference between revisions

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New page: left|200px<br /> <applet load="3ygs" size="450" color="white" frame="true" align="right" spinBox="true" caption="3ygs, resolution 2.5Å" /> '''APAF-1 CARD IN COMPL...
 
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[[Image:3ygs.gif|left|200px]]<br />
<applet load="3ygs" size="450" color="white" frame="true" align="right" spinBox="true"
caption="3ygs, resolution 2.5&Aring;" />
'''APAF-1 CARD IN COMPLEX WITH PRODOMAIN OF PROCASPASE-9'''<br />


==Overview==
==APAF-1 CARD IN COMPLEX WITH PRODOMAIN OF PROCASPASE-9==
Caspase-9-mediated apoptosis (programmed cell death) plays a central role, in the development and homeostasis of all multicellular organisms. Mature, caspase-9 is derived from its procaspase precursor as a result of, recruitment by the activating factor Apaf-1. The crystal structures of the, caspase-recruitment domain of Apaf-1 by itself and in complex with the, prodomain of procaspase-9 have been determined at 1.6 and 2.5 A, resolution, respectively. These structures and other evidence reveal that, each molecule of Apaf-1 interacts with a molecule of procaspase-9 through, two highly charged and complementary surfaces formed by non-conserved, residues; these surfaces determine recognition specificity through, networks of intermolecular hydrogen bonds and van der Waals interactions., Mutation of the important interface residues in procaspase-9 or Apaf-1, prevents or reduces activation of procaspase-9 in a cell-free system., Wild-type, but not mutant, prodomains of caspase-9 completely inhibit, catalytic processing of procaspase-9. Furthermore, analysis of homologues, from Caenorhabditis elegans indicates that recruitment of CED-3 by CED-4, is probably mediated by the same set of conserved structural motifs, with, a corresponding change in the specificity-determining residues.
<StructureSection load='3ygs' size='340' side='right'caption='[[3ygs]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ygs]] is a 2 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=3YGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3YGS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</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=3ygs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ygs OCA], [https://pdbe.org/3ygs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ygs RCSB], [https://www.ebi.ac.uk/pdbsum/3ygs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ygs 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/yg/3ygs_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=3ygs ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Caspase-9-mediated apoptosis (programmed cell death) plays a central role in the development and homeostasis of all multicellular organisms. Mature caspase-9 is derived from its procaspase precursor as a result of recruitment by the activating factor Apaf-1. The crystal structures of the caspase-recruitment domain of Apaf-1 by itself and in complex with the prodomain of procaspase-9 have been determined at 1.6 and 2.5 A resolution, respectively. These structures and other evidence reveal that each molecule of Apaf-1 interacts with a molecule of procaspase-9 through two highly charged and complementary surfaces formed by non-conserved residues; these surfaces determine recognition specificity through networks of intermolecular hydrogen bonds and van der Waals interactions. Mutation of the important interface residues in procaspase-9 or Apaf-1 prevents or reduces activation of procaspase-9 in a cell-free system. Wild-type, but not mutant, prodomains of caspase-9 completely inhibit catalytic processing of procaspase-9. Furthermore, analysis of homologues from Caenorhabditis elegans indicates that recruitment of CED-3 by CED-4 is probably mediated by the same set of conserved structural motifs, with a corresponding change in the specificity-determining residues.


==About this Structure==
Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1.,Qin H, Srinivasula SM, Wu G, Fernandes-Alnemri T, Alnemri ES, Shi Y Nature. 1999 Jun 10;399(6736):549-57. PMID:10376594<ref>PMID:10376594</ref>
3YGS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=3YGS OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1., Qin H, Srinivasula SM, Wu G, Fernandes-Alnemri T, Alnemri ES, Shi Y, Nature. 1999 Jun 10;399(6736):549-57. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10376594 10376594]
</div>
<div class="pdbe-citations 3ygs" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Apoptotic protease-activating factor-1 3D structures|Apoptotic protease-activating factor-1 3D structures]]
*[[Caspase 3D structures|Caspase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Alnemri, E.]]
[[Category: Alnemri E]]
[[Category: Fernandes-Alnemri, T.]]
[[Category: Fernandes-Alnemri T]]
[[Category: Qin, H.]]
[[Category: Qin H]]
[[Category: Shi, Y.]]
[[Category: Shi Y]]
[[Category: Srinivasula, S.]]
[[Category: Srinivasula S]]
[[Category: Wu, G.]]
[[Category: Wu G]]
[[Category: apoptosis]]
[[Category: caspase activation]]
[[Category: caspase recruitment]]
[[Category: recognition complex]]
 
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