Bacterial protein mimics its host to disable a key enzyme

NEW YORK Helicobacter pylori, an infection that causes gastric ulcers and cancers of the gut, may be influenced by a bacterial protein that influences the structure of stomach tissue, scientists found.

C. Erec Stebbins, head of the Laboratory of Structural Microbiology at Rockefeller University, Research Associate Dragana Nesic and colleagues deciphered the atomic structure of an important segment of the large H. pylori protein CagA as it attached to a human enzyme called MARK2. MARK2 (also known as PAR1b) regulates processes, including the "tight junctions" that form between cells, packing stomach tissue together.

The researchers concluded that the protein's make-up was similar to a human protein, but instead, it disrupted different cell functions. By injecting a protein into the stomach lining that mimics a native protein but has its opposite effect, the bacterium shuts down a process that aids the development of the stomach lining, scientists said.

H. pylori is known for its direct involvement in gastric ulcers and tumors, and the activity of the enzyme that CagA effectively shuts down has been implicated in other disorders, including Alzheimer's disease and obesity. Understanding more about how CagA works is potentially useful for treating a litany of medical problems, researchers noted.

"Evolution has created a bacterial protein -- CagA -- that looks exactly like one of ours, and the enzyme that interacts with it is totally fooled," Stebbins said. "CagA binds to it so tightly that the enzyme gets locked in this trapped, dead state and is unable to do what it usually would.

"What we hope is that now we've opened up CagA by showing how we can take this huge protein on," Stebbins added. "We would love to see this kind of research accelerate because there is a lot more we need to understand about how it works."

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