2fp3: Difference between revisions

Revision as of 04:09, 4 May 2008

Crystal structure of the Drosophila initiator caspase Dronc

OverviewOverview

Activation of an initiator caspase is essential to the execution of apoptosis. The molecular mechanisms by which initiator caspases are activated remain poorly understood. Here we demonstrate that the autocatalytic cleavage of Dronc, an important initiator caspase in Drosophila, results in a drastic enhancement of its catalytic activity in vitro. The autocleaved Dronc forms a homodimer, whereas the uncleaved Dronc zymogen exists exclusively as a monomer. Thus the autocatalytic cleavage in Dronc induces its stable dimerization, which presumably allows the two adjacent monomers to mutually stabilize their active sites, leading to activation. Crystal structure of a prodomain-deleted Dronc zymogen, determined at 2.5 A resolution, reveals an unproductive conformation at the active site, which is consistent with the observation that the zymogen remains catalytically inactive. This study revealed insights into mechanism of Dronc activation, and in conjunction with other observations, suggests diverse mechanisms for the activation of initiator caspases.

About this StructureAbout this Structure

2FP3 is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.

ReferenceReference

Structure and activation mechanism of the Drosophila initiator caspase Dronc., Yan N, Huh JR, Schirf V, Demeler B, Hay BA, Shi Y, J Biol Chem. 2006 Mar 31;281(13):8667-74. Epub 2006 Jan 30. PMID:16446367 Page seeded by OCA on Sun May 4 04:09:29 2008

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OCA

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 [[Image:2fp3.gif|left|200px]]
- {{Structure
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-|GENE= Nc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster])
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fp3 OCA], [http://www.ebi.ac.uk/pdbsum/2fp3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fp3 RCSB]</span>
-}}
 '''Crystal structure of the Drosophila initiator caspase Dronc'''
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 [[Category: Shi, Y.]]
 [[Category: Yan, N.]]
-[[Category: active site conformation]]
+[[Category: Active site conformation]]
-[[Category: apoptosis]]
+[[Category: Apoptosis]]
-[[Category: caspase]]
+[[Category: Caspase]]
-[[Category: dimerization]]
+[[Category: Dimerization]]
-[[Category: initiator caspase activation]]
+[[Category: Initiator caspase activation]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 04:09:29 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:05:49 2008''