2fp3: Difference between revisions

Revision as of 18:23, 21 February 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

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-[[Image:2fp3.gif|left|200px]]<br /><applet load="2fp3" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2fp3.gif|left|200px]]<br /><applet load="2fp3" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2fp3, resolution 2.5&Aring;" />
 '''Crystal structure of the Drosophila initiator caspase Dronc'''<br />
 ==Overview==
-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.
+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 Structure==
-FP3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FP3 OCA].
+FP3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FP3 OCA].
 ==Reference==
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 [[Category: initiator caspase activation]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:40:14 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:23:45 2008''