View source for 2p1h

==Rapid Folding and Unfolding of Apaf-1 CARD==
<StructureSection load='2p1h' size='340' side='right' caption='[[2p1h]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2p1h]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The September 2014 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Apoptosomes''  by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2014_9 10.2210/rcsb_pdb/mom_2014_9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P1H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P1H FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APAF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p1h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2p1h RCSB], [http://www.ebi.ac.uk/pdbsum/2p1h PDBsum]</span></td></tr>
</table>
== Function ==
[[http://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/p1/2p1h_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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Caspase recruitment domains (CARDs) are members of the death domain superfamily and contain six antiparallel helices in an alpha-helical Greek key topology. We have examined the equilibrium and kinetic folding of the CARD of Apaf-1 (apoptotic protease activating factor 1), which consists of 97 amino acid residues, at pH 6 and pH 8. The results showed that an apparent two state equilibrium mechanism is not adequate to describe the folding of Apaf-1 CARD at either pH, suggesting the presence of intermediates in equilibrium unfolding. Interestingly, the results showed that the secondary structure is less stable than the tertiary structure, based on the transition mid-points for unfolding. Single mixing and sequential mixing stopped-flow studies showed that Apaf-1 CARD folds and unfolds rapidly and suggest a folding mechanism that contains parallel channels with two unfolded conformations folding to the native conformation. Kinetic simulations show that a slow folding phase is described by a third conformation in the unfolded ensemble that interconverts with one or both unfolded species. Overall, the native ensemble is formed rapidly upon refolding. This is in contrast to other CARDs in which folding appears to be dominated by formation of kinetic traps.

Rapid folding and unfolding of Apaf-1 CARD.,Milam SL, Nicely NI, Feeney B, Mattos C, Clark AC J Mol Biol. 2007 May 25;369(1):290-304. Epub 2007 Mar 15. PMID:17408690<ref>PMID:17408690</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Apoptosomes]]
[[Category: Homo sapiens]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Clark, A C]]
[[Category: Feeney, B]]
[[Category: Mattos, C]]
[[Category: Milam, S L]]
[[Category: Nicely, N I]]
[[Category: Apaf-1]]
[[Category: Apoptosis]]
[[Category: Folding]]
[[Category: Unfolding]]