5 years ago

Functional interaction and structural characteristics of unique components of Helicobacter pylori T4SS

Functional interaction and structural characteristics of unique components of Helicobacter pylori T4SS
Marcos Flores-Encarnación, Enrique Merino, Germán Rubén Aguilar-Gutiérrez
The Helicobacter pylori infection of the human gastric mucosa causes chronic active gastritis and peptic ulcers and is associated with the development of gastric cancer. Epidemiological studies show that these gastric diseases are related to virulent H. pylori strains that harbor the cytotoxin-associated gene pathogenicity island (cag PAI). The cag PAI is a DNA insertion in the H. pylori chromosome that encodes ~ 27 proteins, including the oncoprotein CagA. Approximately 20 of these proteins have been designated as cag type IV secretion system (T4SS) components. However, only 11 of these proteins share function, structure, and/or sequence similarities with the prototypical VirB/VirD4 T4SS of Agrobacterium tumefaciens. The VirB/VirD4 orthologs of the cag T4SS of H. pylori are required for CagA translocation and stimulate the gastric epithelial cells to produce and secrete interleukin-8 (IL-8). The cag PAI encodes eight additional proteins, such as Cag3 (Cagδ/HP0522), CagM (Cag16/HP0537), CagU (Cag11/HP0531), CagI (Cag19/HP0540), and CagH (Cag20/HP0541), which are also required for the translocation of CagA and IL-8 secretion, meanwhile CagF (Cag22/HP0543), CagG (Cag21/HP0542), and CagZ (Cag6/HP0526) are just required for the translocation of CagA. However, relatively little is known about their functions and structural organization because they exhibit a nondetectable sequence similarity with T4SS components in the current databases. In this review, we conducted an exhaustive analysis of the literature to present the biochemistry, putative role, localization, and interactions of each of these eight additional cag T4SS components. The virulent Helicobacter pylori strains harbor a cytotoxin-associated gene (cag) type IV secretion system (T4SS). The cag T4SS requires 11 proteins that present orthology with those components of the prototypical Agrobacterium tumefaciens VirB/VirD4 T4SS to inject the oncoprotein CagA. The cag T4SS also requires eight additional proteins to be functional. This review summarizes what is known about these eight additional cag T4SS components.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/febs.14092

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