1i3p
From Proteopedia
(New page: 200px<br /><applet load="1i3p" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i3p, resolution 3.10Å" /> '''THE 3.1 ANGSTROM RES...) |
Revision as of 11:07, 21 February 2008
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THE 3.1 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF A MUTATED BACULOVIRUS P35 AFTER CASPASE CLEAVAGE
Overview
Baculovirus P35 is a universal suppressor of apoptosis that stoichiometrically inhibits cellular caspases in a novel cleavage-dependent mechanism. Upon caspase cleavage at Asp-87, the 10- and 25-kDa cleavage products of P35 remain tightly associated with the inhibited caspase. Mutations in the alpha-helix of the reactive site loop preceding the cleavage site abrogate caspase inhibition and antiapoptotic activity. Substitution of Pro for Val-71, which is located in the middle of this alpha-helix, produces a protein that is cleaved at the requisite Asp-87 but does not remain bound to the caspase. This loss-of-function mutation provided the opportunity to structurally analyze the conformational changes of the P35 reactive site loop after caspase cleavage. We report here the 2.7 A resolution crystal structure of V71P-mutated P35 after cleavage by human caspase-3. The structure reveals a large movement in the carboxyl-terminal side of the reactive site loop that swings down and forms a new beta-strand that augments an existing beta-sheet. Additionally, the hydrophobic amino terminus releases and extends away from the protein core. Similar movements occur when P35 forms an inhibitory complex with human caspase-8. These findings suggest that the alpha-helix mutation may alter the sequential steps or kinetics of the conformational changes required for inhibition, thereby causing P35 loss of function.
About this Structure
1I3P is a Single protein structure of sequence from Autographa californica nucleopolyhedrovirus. Full crystallographic information is available from OCA.
Reference
Crystal structure of baculovirus P35 reveals a novel conformational change in the reactive site loop after caspase cleavage., dela Cruz WP, Friesen PD, Fisher AJ, J Biol Chem. 2001 Aug 31;276(35):32933-9. Epub 2001 Jun 11. PMID:11402050
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