Two substrate‐targeting sites in the Yersinia protein tyrosine phosphatase co‐operate to promote bacterial virulence
Summary YopH 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 epithelia...
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Published in | Molecular microbiology Vol. 55; no. 5; pp. 1346 - 1356 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Science Ltd
01.03.2005
Blackwell Science Blackwell Publishing Ltd |
Subjects | |
Online Access | Get full text |
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Summary: | Summary
YopH 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. |
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Bibliography: | Department of Biochemistry, University of Utah, Salt Lake City, UT 84132, USA. Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109‐2216, USA ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0950-382X 1365-2958 |
DOI: | 10.1111/j.1365-2958.2005.04477.x |