The main goal of this project is to structurally and functionally characterize the molecular interactions underlying infection by the common gastric pathogen H. pylori. This will not only lead to a better understanding of the fundamental molecular recogni tion mechanisms, but also put us in a position to develop new tools for disease intervention. This project is part of a broader investigation by us, directed at the role of blood group antigens in pathogenesis, as the blood group of individuals has been s hown to correlate with the severity of disease in a number of bacterial infections. Understanding the underlying molecular recognition processes may eventually provide us with important leads towards patient-specific treatment and prevention strategies.
This project is very challenging, as it deals with the structure determination of membrane proteins. Membrane protein structure determination has two major bottlenecks: the production of the protein sample in sufficient amounts and protein crystallization . In this case, protein production is a minor issue, at least for BabA, as 30% of the total protein content of H. pylori consists of BabA, its major blood group antigen binding adhesin. However, membrane protein crystallization is notoriously difficult an d membrane protein crystals are often of inferior quality, making extensive synchrotron use a necessity. This project will pave the way to the establishment of membrane protein crystallography in Norway.