DOI: 10.1111/j.1365-2958.2005.04477.x. Two substrate‐targeting sites in the <i>Yersinia</i> protein tyrosine phosphatase co‐operate to promote bacterial virulence

Two substrate‐targeting sites in the Yersinia protein tyrosine phosphatase co‐operate to promote bacterial virulence

10.1111/j.1365-2958.2005.04477.x

Crossref journal-article

Wiley

Molecular Microbiology (311)

Abstract

SummaryYopH is a protein tyrosine phosphatase and an essential virulence determinant of the pathogenic bacterium Yersinia. Yersinia delivers YopH into infected host cells using a type III secretion mechanism. YopH dephosphorylates several focal adhesion proteins including p130Cas in human epithelial cells, resulting in disruption of focal adhesions and cell detachment from the extracellular matrix. How the C‐terminal protein tyrosine phosphatase domain of YopH targets specific substrates such as p130Cas in the complex milieu of the host cell has not been fully elucidated. An N‐terminal non‐catalytic domain of YopH binds p130Cas in a phosphotyrosine‐dependent manner and functions as a novel substrate‐targeting site. The structure of the YopH protein tyrosine phosphatase domain bound to a model phosphopeptide substrate was solved and the resulting structure revealed a second substrate‐targeting site (‘site 2’) within the catalytic domain. Site 2 binds to p130Cas in a phosphotyrosine‐dependent manner, and co‐operates with the N‐terminal domain (‘site 1’) to promote efficient recognition of p130Cas by YopH in epithelial cells. The identification of two substrate‐targeting sites in YopH that co‐operate to promote epithelial cell detachment and bacterial virulence reinforces the importance of protein–protein interactions for determining protein tyrosine phosphatase specificity in vivo, and highlights the sophisticated nature of microbial pathogenicity factors.

Bibliography

Ivanov, M. I., Stuckey, J. A., Schubert, H. L., Saper, M. A., & Bliska, J. B. (2005). Two substrateâtargeting sites in the Yersinia protein tyrosine phosphatase coâoperate to promote bacterial virulence. Molecular Microbiology, 55(5), 1346â1356. Portico.

Authors 5

Maya I. Ivanov (first)
Jeanne A. Stuckey (additional)
Heidi L. Schubert (additional)
Mark A. Saper (additional)
James B. Bliska (additional)

References 34 Referenced 40

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Dates

Type	When
Created	20 years, 6 months ago (Feb. 17, 2005, 10:17 a.m.)
Deposited	1 year, 10 months ago (Oct. 11, 2023, 8:52 a.m.)
Indexed	3 months ago (June 4, 2025, 6:29 a.m.)
Issued	20 years, 7 months ago (Feb. 4, 2005)
Published	20 years, 7 months ago (Feb. 4, 2005)
Published Online	20 years, 7 months ago (Feb. 4, 2005)
Published Print	20 years, 6 months ago (March 1, 2005)

Funders 0

None

BibTeX

@article{Ivanov_2005, title={Two substrate‐targeting sites in the Yersinia protein tyrosine phosphatase co‐operate to promote bacterial virulence}, volume={55}, ISSN={1365-2958}, url={http://dx.doi.org/10.1111/j.1365-2958.2005.04477.x}, DOI={10.1111/j.1365-2958.2005.04477.x}, number={5}, journal={Molecular Microbiology}, publisher={Wiley}, author={Ivanov, Maya I. and Stuckey, Jeanne A. and Schubert, Heidi L. and Saper, Mark A. and Bliska, James B.}, year={2005}, month=feb, pages={1346–1356} }

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