Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates.
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Nesic D, Miller MC, Quinkert ZT, Stein M, Chait BT, Stebbins CE
Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates.
Nat Struct Mol Biol. 2010 Jan;17(1):130-2. doi: 10.1038/nsmb.1705. Epub 2009 Dec 6.
- PubMed ID
- 19966800 [ View in PubMed]
- 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.