Structural analysis of the molecular machinery involved in protein secretion, membrane protein assembly and protein processing

The ability for proteins to travel across cell membranes is critical to the life of all cells, yet research shows that bacterial cells differ from human cells in some of the components necessary for this movement to occur. In previous work supported by an MSFHR Scholar award, Dr. Mark Paetzel uncovered the three-dimensional structure of proteins that make up the molecular machinery involved in this movement in bacterial cells. Now a Senior Scholar, Dr. Paetzel will continue this work with the goal of learning more about these structures in order to determine how to inhibit the movement of proteins across cell membranes in bacteria. He will use X-ray crystallography to investigate the proteins involved in protein targeting, translocation, and membrane protein assembly in bacteria. Dr. Paetzel is also investigating a particular enzyme that functions at the membrane surface — one that causes the cleaving of interior peptide bonds in a protein. Understanding how to inhibit this enzyme and its role in bacterial cell movement could lead to the development of a novel class of antibiotics — a strategy that is required to meet the ever-increasing challenge of antibiotic resistance.