Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates.
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.
Nesić
Dragana
D
Laboratory of Structural Microbiology, Rockefeller University, New York, New York, USA.
Miller
Marshall C
MC
Quinkert
Zachary T
ZT
Stein
Markus
M
Chait
Brian T
BT
Stebbins
C Erec
CE
D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002850:Chromatography, Gel; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D016296:Mutagenesis; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; C094670:MARK2 protein, human; D017346:Protein Serine-Threonine Kinases