2h7v

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(New page: 200px<br /> <applet load="2h7v" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h7v, resolution 2.600&Aring;" /> '''Co-crystal structu...)
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[[Image:2h7v.gif|left|200px]]<br />
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[[Image:2h7v.gif|left|200px]]<br /><applet load="2h7v" size="350" color="white" frame="true" align="right" spinBox="true"
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<applet load="2h7v" size="450" color="white" frame="true" align="right" spinBox="true"
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caption="2h7v, resolution 2.600&Aring;" />
caption="2h7v, resolution 2.600&Aring;" />
'''Co-crystal structure of YpkA-Rac1'''<br />
'''Co-crystal structure of YpkA-Rac1'''<br />
==Overview==
==Overview==
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Yersinia spp. cause gastroenteritis and the plague, representing, historically devastating pathogens that are currently an important, biodefense and antibiotic resistance concern. A critical virulence, determinant is the Yersinia protein kinase A, or YpkA, a multidomain, protein that disrupts the eukaryotic actin cytoskeleton. Here we solve the, crystal structure of a YpkA-Rac1 complex and find that YpkA possesses a, Rac1 binding domain that mimics host guanidine nucleotide dissociation, inhibitors (GDIs) of the Rho GTPases. YpkA inhibits nucleotide exchange in, Rac1 and RhoA, and mutations that disrupt the YpkA-GTPase interface, abolish this activity in vitro and impair in vivo YpkA-induced, cytoskeletal disruption. In cell culture experiments, the kinase and the, GDI domains of YpkA act synergistically to promote cytoskeletal, disruption, and a Y. pseudotuberculosis mutant lacking YpkA GDI activity, shows attenuated virulence in a mouse infection assay. We conclude that, virulence in Yersinia depends strongly upon mimicry of host GDI proteins, by YpkA.
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Yersinia spp. cause gastroenteritis and the plague, representing historically devastating pathogens that are currently an important biodefense and antibiotic resistance concern. A critical virulence determinant is the Yersinia protein kinase A, or YpkA, a multidomain protein that disrupts the eukaryotic actin cytoskeleton. Here we solve the crystal structure of a YpkA-Rac1 complex and find that YpkA possesses a Rac1 binding domain that mimics host guanidine nucleotide dissociation inhibitors (GDIs) of the Rho GTPases. YpkA inhibits nucleotide exchange in Rac1 and RhoA, and mutations that disrupt the YpkA-GTPase interface abolish this activity in vitro and impair in vivo YpkA-induced cytoskeletal disruption. In cell culture experiments, the kinase and the GDI domains of YpkA act synergistically to promote cytoskeletal disruption, and a Y. pseudotuberculosis mutant lacking YpkA GDI activity shows attenuated virulence in a mouse infection assay. We conclude that virulence in Yersinia depends strongly upon mimicry of host GDI proteins by YpkA.
==About this Structure==
==About this Structure==
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2H7V is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Yersinia_pseudotuberculosis Yersinia pseudotuberculosis] with MG and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2H7V OCA].
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2H7V is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Yersinia_pseudotuberculosis Yersinia pseudotuberculosis] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H7V OCA].
==Reference==
==Reference==
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[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Yersinia pseudotuberculosis]]
[[Category: Yersinia pseudotuberculosis]]
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[[Category: Bliska, J.B.]]
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[[Category: Bliska, J B.]]
[[Category: Ivanov, M.]]
[[Category: Ivanov, M.]]
[[Category: Prehna, G.]]
[[Category: Prehna, G.]]
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[[Category: Stebbins, C.E.]]
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[[Category: Stebbins, C E.]]
[[Category: GDP]]
[[Category: GDP]]
[[Category: MG]]
[[Category: MG]]
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[[Category: ypka]]
[[Category: ypka]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:28:12 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:39:06 2008''

Revision as of 15:39, 21 February 2008


2h7v, resolution 2.600Å

Drag the structure with the mouse to rotate

Co-crystal structure of YpkA-Rac1

Overview

Yersinia spp. cause gastroenteritis and the plague, representing historically devastating pathogens that are currently an important biodefense and antibiotic resistance concern. A critical virulence determinant is the Yersinia protein kinase A, or YpkA, a multidomain protein that disrupts the eukaryotic actin cytoskeleton. Here we solve the crystal structure of a YpkA-Rac1 complex and find that YpkA possesses a Rac1 binding domain that mimics host guanidine nucleotide dissociation inhibitors (GDIs) of the Rho GTPases. YpkA inhibits nucleotide exchange in Rac1 and RhoA, and mutations that disrupt the YpkA-GTPase interface abolish this activity in vitro and impair in vivo YpkA-induced cytoskeletal disruption. In cell culture experiments, the kinase and the GDI domains of YpkA act synergistically to promote cytoskeletal disruption, and a Y. pseudotuberculosis mutant lacking YpkA GDI activity shows attenuated virulence in a mouse infection assay. We conclude that virulence in Yersinia depends strongly upon mimicry of host GDI proteins by YpkA.

About this Structure

2H7V is a Protein complex structure of sequences from Homo sapiens and Yersinia pseudotuberculosis with and as ligands. Full crystallographic information is available from OCA.

Reference

Yersinia virulence depends on mimicry of host Rho-family nucleotide dissociation inhibitors., Prehna G, Ivanov MI, Bliska JB, Stebbins CE, Cell. 2006 Sep 8;126(5):869-80. PMID:16959567

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