AsianScientist (Nov. 3, 2016) – Researchers in Japan have found that variations in a particular region of the cancer-causing protein CagA are linked to the degree of damage that Helicobacter pylori bacteria cause to the mucous membrane lining of the stomach. The study was published in Scientific Reports.
During infection, H. pylori bacteria inject CagA protein directly into cells of the human stomach mucous membrane. H. pylori infection can lead to the development of gastrointestinal diseases such as atrophic gastritis, peptic ulceration, and gastric cancer. These H. pylori-associated diseases are extremely common in the East Asian countries of Japan, China, and South Korea.
Interestingly, there is a substantial difference in the structure of CagA between H. pylori strains circulating in East Asian countries and those circulating in the rest of the world. This suggests that the ability of CagA to cause injury to the stomach could be related to the structural difference of the protein from one H. pylori strain to another.
Through a quantitative approach, the research team of Professor Masanori Hatakeyama at the Graduate School of Medicine, the University of Tokyo, found that a sequence in CagA termed the CagA multimerization (CM) motif influences the strength of interaction between CagA and its cellular target, the protein PAR1b.
Western-type CagA species contain variable copies of Western-specific CM motif. The strength with which Western CagA bound to Par1b was proportional to the number of copies of these CM motifs. In addition, East Asian CagA species, which usually only contain a single copy of the East Asian-specific CM motif, bound to PAR1b to a similar degree as Western CagA containing two Western-specific CM.
These results led the research team to conclude that it is differences in the structure of the CM motif in the H. pylori protein CagA that determine the degree of injury to the gastric mucous lining caused by H. pylori.
“We were very excited to learn that a few amino acid alterations in CagA, the factor through which H. pylori causes damage to the stomach, may give rise to quite different clinical outcomes,” said Hatakeyama.
The article can be found at: Nishikawa et al. (2016) Impact of Structural Polymorphism for the Helicobacter Pylori CagA Oncoprotein on Binding to Polarity-Regulating Kinase PAR1b.
———
Source: University of Tokyo.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
