Structure-based analysis of pathogenic activity of Helicobacter pylori CagA

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Helicobacter pylori CagA protein is injected into gastric epithelial cells, where it interacts with cellular proteins such as SHP-2 and PAR1. CagA perturbs intracellular machineries involved in the regulation of cell growth and cell polarity through its C-terminal region containing Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs. To elucidate molecular basis for the pathogenic activity of CagA, we sought to determine three-dimensional structure of CagA. From results of proteolysis experiment, we found that CagA consists of the possible N-terminal and C-terminal structural domains. The CagA C-terminal fragment largely consists of an unfolded structure, although the fragment possesses an ability to bind with target molecules. Furthermore, at results of X-ray crystallographic analysis, the CagA N-terminal fragment indicate that the region has a structure comprised of three domains.