1hy5
From Proteopedia
(New page: 200px<br /><applet load="1hy5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hy5, resolution 2.25Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1hy5.gif|left|200px]]<br /><applet load="1hy5" size=" | + | [[Image:1hy5.gif|left|200px]]<br /><applet load="1hy5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1hy5, resolution 2.25Å" /> | caption="1hy5, resolution 2.25Å" /> | ||
'''CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF YOPE-YERSINIA PESTIS GAP EFFECTOR PROTEIN.'''<br /> | '''CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF YOPE-YERSINIA PESTIS GAP EFFECTOR PROTEIN.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Yersinia pestis, the causative agent of bubonic plague, evades the immune | + | Yersinia pestis, the causative agent of bubonic plague, evades the immune response of the infected organism by using a type III (contact-dependent) secretion system to deliver effector proteins into the cytosol of mammalian cells, where they interfere with signaling pathways that regulate inflammation and cytoskeleton dynamics. The cytotoxic effector YopE functions as a potent GTPase-activating protein (GAP) for Rho family GTP-binding proteins, including RhoA, Rac1, and Cdc42. Down-regulation of these molecular switches results in the loss of cell motility and inhibition of phagocytosis, enabling Y. pestis to thrive on the surface of macrophages. We have determined the crystal structure of the GAP domain of YopE (YopE(GAP); residues 90-219) at 2.2-A resolution. Apart from the fact that it is composed almost entirely of alpha-helices, YopE(GAP) shows no obvious structural similarity with eukaryotic RhoGAP domains. Moreover, unlike the catalytically equivalent arginine fingers of the eukaryotic GAPs, which are invariably contained within flexible loops, the critical arginine in YopE(GAP) (Arg144) is part of an alpha-helix. The structure of YopE(GAP) is strikingly similar to the GAP domains from Pseudomonas aeruginosa (ExoS(GAP)) and Salmonella enterica (SptP(GAP)), despite the fact that the three amino acid sequences are not highly conserved. A comparison of the YopE(GAP) structure with those of the Rac1-ExoS(GAP) and Rac1-SptP complexes indicates that few, if any, significant conformational changes occur in YopE(GAP) when it interacts with its G protein targets. The structure of YopE(GAP) may provide an avenue for the development of novel therapeutic agents to combat plague. |
==About this Structure== | ==About this Structure== | ||
| - | 1HY5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Yersinia_pestis Yersinia pestis]. Full crystallographic information is available from [http:// | + | 1HY5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Yersinia_pestis Yersinia pestis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HY5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Yersinia pestis]] | [[Category: Yersinia pestis]] | ||
| - | [[Category: Evdokimov, A | + | [[Category: Evdokimov, A G.]] |
| - | [[Category: Routzahn, K | + | [[Category: Routzahn, K M.]] |
| - | [[Category: Tropea, J | + | [[Category: Tropea, J E.]] |
| - | [[Category: Waugh, D | + | [[Category: Waugh, D S.]] |
[[Category: arginine finger]] | [[Category: arginine finger]] | ||
[[Category: beta hairpin]] | [[Category: beta hairpin]] | ||
[[Category: four helix up-down-up-down antiparallel bundle]] | [[Category: four helix up-down-up-down antiparallel bundle]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:06:02 2008'' |
Revision as of 11:06, 21 February 2008
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CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF YOPE-YERSINIA PESTIS GAP EFFECTOR PROTEIN.
Overview
Yersinia pestis, the causative agent of bubonic plague, evades the immune response of the infected organism by using a type III (contact-dependent) secretion system to deliver effector proteins into the cytosol of mammalian cells, where they interfere with signaling pathways that regulate inflammation and cytoskeleton dynamics. The cytotoxic effector YopE functions as a potent GTPase-activating protein (GAP) for Rho family GTP-binding proteins, including RhoA, Rac1, and Cdc42. Down-regulation of these molecular switches results in the loss of cell motility and inhibition of phagocytosis, enabling Y. pestis to thrive on the surface of macrophages. We have determined the crystal structure of the GAP domain of YopE (YopE(GAP); residues 90-219) at 2.2-A resolution. Apart from the fact that it is composed almost entirely of alpha-helices, YopE(GAP) shows no obvious structural similarity with eukaryotic RhoGAP domains. Moreover, unlike the catalytically equivalent arginine fingers of the eukaryotic GAPs, which are invariably contained within flexible loops, the critical arginine in YopE(GAP) (Arg144) is part of an alpha-helix. The structure of YopE(GAP) is strikingly similar to the GAP domains from Pseudomonas aeruginosa (ExoS(GAP)) and Salmonella enterica (SptP(GAP)), despite the fact that the three amino acid sequences are not highly conserved. A comparison of the YopE(GAP) structure with those of the Rac1-ExoS(GAP) and Rac1-SptP complexes indicates that few, if any, significant conformational changes occur in YopE(GAP) when it interacts with its G protein targets. The structure of YopE(GAP) may provide an avenue for the development of novel therapeutic agents to combat plague.
About this Structure
1HY5 is a Single protein structure of sequence from Yersinia pestis. Full crystallographic information is available from OCA.
Reference
Crystal structure of the Yersinia pestis GTPase activator YopE., Evdokimov AG, Tropea JE, Routzahn KM, Waugh DS, Protein Sci. 2002 Feb;11(2):401-8. PMID:11790850
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