2ar9
From Proteopedia
(New page: 200px<br /> <applet load="2ar9" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ar9, resolution 2.8Å" /> '''Crystal structure of...) |
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| - | [[Image:2ar9.gif|left|200px]]<br /> | + | [[Image:2ar9.gif|left|200px]]<br /><applet load="2ar9" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2ar9" size=" | + | |
caption="2ar9, resolution 2.8Å" /> | caption="2ar9, resolution 2.8Å" /> | ||
'''Crystal structure of a dimeric caspase-9'''<br /> | '''Crystal structure of a dimeric caspase-9'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Caspases are responsible for the execution of programmed cell death | + | Caspases are responsible for the execution of programmed cell death (apoptosis) and must undergo proteolytic activation, in response to apoptotic stimuli, to function. The mechanism of initiator caspase activation has been generalized by the induced proximity model, which is thought to drive dimerization-mediated activation of caspases. The initiator caspase, caspase-9, exists predominantly as a monomer in solution. To examine the induced proximity model, we engineered a constitutively dimeric caspase-9 by relieving steric hindrance at the dimer interface. Crystal structure of the engineered caspase-9 closely resembles that of the wild-type (WT) caspase-9, including all relevant structural details and the asymmetric nature of two monomers. Compared to the WT caspase-9, this engineered dimer exhibits a higher level of catalytic activity in vitro and induces more efficient cell death when expressed. However, the catalytic activity of the dimeric caspase-9 is only a small fraction of that for the Apaf-1-activated caspase-9. Furthermore, in contrast to the WT caspase-9, the activity of the dimeric caspase-9 can no longer be significantly enhanced in an Apaf-1-dependent manner. These findings suggest that dimerization of caspase-9 may be qualitatively different from its activation by Apaf-1, and in conjunction with other evidence, posit an induced conformation model for the activation of initiator caspases. |
==About this Structure== | ==About this Structure== | ||
| - | 2AR9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with DMR as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2AR9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=DMR:'>DMR</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AR9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Chao, Y.]] | [[Category: Chao, Y.]] | ||
[[Category: Fairman, R.]] | [[Category: Fairman, R.]] | ||
| - | [[Category: Rigotti, D | + | [[Category: Rigotti, D J.]] |
[[Category: Shi, Y.]] | [[Category: Shi, Y.]] | ||
| - | [[Category: Shiozaki, E | + | [[Category: Shiozaki, E N.]] |
| - | [[Category: Srinivassula, S | + | [[Category: Srinivassula, S M.]] |
[[Category: DMR]] | [[Category: DMR]] | ||
[[Category: caspase]] | [[Category: caspase]] | ||
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[[Category: initiator caspase]] | [[Category: initiator caspase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:30:09 2008'' |
Revision as of 14:30, 21 February 2008
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Crystal structure of a dimeric caspase-9
Overview
Caspases are responsible for the execution of programmed cell death (apoptosis) and must undergo proteolytic activation, in response to apoptotic stimuli, to function. The mechanism of initiator caspase activation has been generalized by the induced proximity model, which is thought to drive dimerization-mediated activation of caspases. The initiator caspase, caspase-9, exists predominantly as a monomer in solution. To examine the induced proximity model, we engineered a constitutively dimeric caspase-9 by relieving steric hindrance at the dimer interface. Crystal structure of the engineered caspase-9 closely resembles that of the wild-type (WT) caspase-9, including all relevant structural details and the asymmetric nature of two monomers. Compared to the WT caspase-9, this engineered dimer exhibits a higher level of catalytic activity in vitro and induces more efficient cell death when expressed. However, the catalytic activity of the dimeric caspase-9 is only a small fraction of that for the Apaf-1-activated caspase-9. Furthermore, in contrast to the WT caspase-9, the activity of the dimeric caspase-9 can no longer be significantly enhanced in an Apaf-1-dependent manner. These findings suggest that dimerization of caspase-9 may be qualitatively different from its activation by Apaf-1, and in conjunction with other evidence, posit an induced conformation model for the activation of initiator caspases.
About this Structure
2AR9 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Engineering a dimeric caspase-9: a re-evaluation of the induced proximity model for caspase activation., Chao Y, Shiozaki EN, Srinivasula SM, Rigotti DJ, Fairman R, Shi Y, PLoS Biol. 2005 Jun;3(6):e183. Epub 2005 May 10. PMID:15941357
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