Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates

Dragana Nešić; Marshall C. Miller; Zachary T. Quinkert; Markus Stein; Brian T. Chait; C. Erec Stebbins

doi:10.1038/nsmb.1705

Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates

Dragana Nešić
, Marshall C. Miller
, Zachary T. Quinkert
, Markus Stein
, Brian T. Chait
, C. Erec Stebbins

Geriatric and General Medicine

Rockefeller University
University of Alberta

Research output: Contribution to journal › Article › peer-review

117 Scopus citations

Abstract

The CagA protein of Helicobacter pylori interacts with numerous cellular factors and is associated with increased virulence and risk of gastric carcinoma. We present here the cocrystal structure of a subdomain of CagA with the human kinase PAR1b/MARK2, revealing that a CagA peptide mimics substrates of this kinase family, resembling eukaryotic protein kinase inhibitors. Mutagenesis of conserved residues central to this interaction renders CagA inactive as an inhibitor of MARK2.

Original language	English
Pages (from-to)	130-132
Number of pages	3
Journal	Nature Structural and Molecular Biology
Volume	17
Issue number	1
DOIs	https://doi.org/10.1038/nsmb.1705
State	Published - Jan 2010

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abstract = "The CagA protein of Helicobacter pylori interacts with numerous cellular factors and is associated with increased virulence and risk of gastric carcinoma. We present here the cocrystal structure of a subdomain of CagA with the human kinase PAR1b/MARK2, revealing that a CagA peptide mimics substrates of this kinase family, resembling eukaryotic protein kinase inhibitors. Mutagenesis of conserved residues central to this interaction renders CagA inactive as an inhibitor of MARK2.",

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AU - Chait, Brian T.

AU - Stebbins, C. Erec

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AB - The CagA protein of Helicobacter pylori interacts with numerous cellular factors and is associated with increased virulence and risk of gastric carcinoma. We present here the cocrystal structure of a subdomain of CagA with the human kinase PAR1b/MARK2, revealing that a CagA peptide mimics substrates of this kinase family, resembling eukaryotic protein kinase inhibitors. Mutagenesis of conserved residues central to this interaction renders CagA inactive as an inhibitor of MARK2.

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Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates

Abstract

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