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2p1h

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Revision as of 05:24, 11 September 2015

Rapid Folding and Unfolding of Apaf-1 CARD

Structural highlights

2p1h is a 1 chain structure with sequence from Human. The September 2014 RCSB PDB Molecule of the Month feature on Apoptosomes by David Goodsell is 10.2210/rcsb_pdb/mom_2014_9. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	APAF1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Milam SL, Nicely NI, Feeney B, Mattos C, Clark AC. Rapid folding and unfolding of Apaf-1 CARD. J Mol Biol. 2007 May 25;369(1):290-304. Epub 2007 Mar 15. PMID:17408690 doi:http://dx.doi.org/10.1016/j.jmb.2007.02.105

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2p1h"

@@ Line 2: / Line 2: @@
 <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>
+<table><tr><td colspan='2'>[[2p1h]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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='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 HUMAN])</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>
+<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://pdbe.org/2p1h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p1h RCSB], [http://www.ebi.ac.uk/pdbsum/2p1h PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 27: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2p1h" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 32: / Line 33: @@
 </StructureSection>
 [[Category: Apoptosomes]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: RCSB PDB Molecule of the Month]]
 [[Category: Clark, A C]]

2p1h

From Proteopedia

Revision as of 05:24, 11 September 2015

Rapid Folding and Unfolding of Apaf-1 CARD

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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