1f0c
From Proteopedia
(New page: 200px<br /><applet load="1f0c" size="450" color="white" frame="true" align="right" spinBox="true" caption="1f0c, resolution 2.26Å" /> '''STRUCTURE OF THE VIR...) |
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| - | [[Image:1f0c.gif|left|200px]]<br /><applet load="1f0c" size=" | + | [[Image:1f0c.gif|left|200px]]<br /><applet load="1f0c" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1f0c, resolution 2.26Å" /> | caption="1f0c, resolution 2.26Å" /> | ||
'''STRUCTURE OF THE VIRAL SERPIN CRMA'''<br /> | '''STRUCTURE OF THE VIRAL SERPIN CRMA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Cowpox virus expresses the serpin CrmA (cytokine response | + | BACKGROUND: Cowpox virus expresses the serpin CrmA (cytokine response modifier A) in order to avoid inflammatory and apoptotic responses of infected host cells. The targets of CrmA are members of the caspase family of proteases that either initiate the extrinsic pathway of apoptosis (caspases 8 and 10) or trigger activation of the pro-inflammatory cytokines interleukin-1beta and interleukin-18 (caspase 1). RESULTS: We have determined the structure of a cleaved form of CrmA to 2.26 A resolution. CrmA has the typical fold of a cleaved serpin, even though it lacks the N-terminal half of the A helix, the entire D helix, and a portion of the E helix that are present in all other known serpins. The reactive-site loop of CrmA was mutated to contain the optimal substrate recognition sequence for caspase 3; however, the mutation only marginally increased the ability of CrmA to inhibit caspase 3. Superposition of the reactive-site loop of alpha1-proteinase inhibitor on the cleaved CrmA structure provides a model for virgin CrmA that can be docked to caspase 1, but not to caspase 3. CONCLUSIONS: CrmA exemplifies viral economy, selective pressure having resulted in a 'minimal' serpin that lacks the regions not needed for structural integrity or inhibitory activity. The docking model provides an explanation for the selectivity of CrmA. Our demonstration that engineering optimal substrate recognition sequences into the CrmA reactive-site loop fails to generate a good caspase 3 inhibitor is consistent with the docking model. |
==About this Structure== | ==About this Structure== | ||
| - | 1F0C is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Cow_pox_virus Cow pox virus] with DTT as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1F0C is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Cow_pox_virus Cow pox virus] with <scene name='pdbligand=DTT:'>DTT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F0C OCA]. |
==Reference== | ==Reference== | ||
| Line 13: | Line 13: | ||
[[Category: Cow pox virus]] | [[Category: Cow pox virus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Bankston, L | + | [[Category: Bankston, L A.]] |
| - | [[Category: Liddington, R | + | [[Category: Liddington, R C.]] |
[[Category: Renatus, M.]] | [[Category: Renatus, M.]] | ||
| - | [[Category: Salvesen, G | + | [[Category: Salvesen, G S.]] |
| - | [[Category: Snipas, S | + | [[Category: Snipas, S J.]] |
| - | [[Category: Stennicke, H | + | [[Category: Stennicke, H R.]] |
[[Category: Turk, D.]] | [[Category: Turk, D.]] | ||
[[Category: Zhou, Q.]] | [[Category: Zhou, Q.]] | ||
| Line 27: | Line 27: | ||
[[Category: serpin]] | [[Category: serpin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:33:26 2008'' |
Revision as of 10:33, 21 February 2008
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STRUCTURE OF THE VIRAL SERPIN CRMA
Overview
BACKGROUND: Cowpox virus expresses the serpin CrmA (cytokine response modifier A) in order to avoid inflammatory and apoptotic responses of infected host cells. The targets of CrmA are members of the caspase family of proteases that either initiate the extrinsic pathway of apoptosis (caspases 8 and 10) or trigger activation of the pro-inflammatory cytokines interleukin-1beta and interleukin-18 (caspase 1). RESULTS: We have determined the structure of a cleaved form of CrmA to 2.26 A resolution. CrmA has the typical fold of a cleaved serpin, even though it lacks the N-terminal half of the A helix, the entire D helix, and a portion of the E helix that are present in all other known serpins. The reactive-site loop of CrmA was mutated to contain the optimal substrate recognition sequence for caspase 3; however, the mutation only marginally increased the ability of CrmA to inhibit caspase 3. Superposition of the reactive-site loop of alpha1-proteinase inhibitor on the cleaved CrmA structure provides a model for virgin CrmA that can be docked to caspase 1, but not to caspase 3. CONCLUSIONS: CrmA exemplifies viral economy, selective pressure having resulted in a 'minimal' serpin that lacks the regions not needed for structural integrity or inhibitory activity. The docking model provides an explanation for the selectivity of CrmA. Our demonstration that engineering optimal substrate recognition sequences into the CrmA reactive-site loop fails to generate a good caspase 3 inhibitor is consistent with the docking model.
About this Structure
1F0C is a Protein complex structure of sequences from Cow pox virus with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of the apoptotic suppressor CrmA in its cleaved form., Renatus M, Zhou Q, Stennicke HR, Snipas SJ, Turk D, Bankston LA, Liddington RC, Salvesen GS, Structure. 2000 Jul 15;8(7):789-97. PMID:10903953
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