Professor, Department of Biology
Massachusetts Institute of Technology
Investigator, Howard Hughes Medical Institute
Host: Lars Dietrich
Title: "Specificity and evolution of protein-protein interactions"
Abstract: Protein-protein interactions are critical to the operation and functions of all cells. The specificity of these interactions is often dictated at the level of molecular recognition, meaning proteins have an intrinsic ability to discriminate cognate from non-cognate partners. Understanding precisely how this discrimination is accomplished remains a major problem, particularly for paralogous protein families in which the individual members share high sequence and structural similarity. Our work tackles this problem primarily in the context of two-component signal transduction systems, the predominant form of signaling in bacteria, and more recently with toxin-antitoxin systems, also found throughout the bacterial kingdom. I will describe our work using analyses of amino acid coevolution to pinpoint the molecular basis of specificity in these proteins. This work has enabled the rational rewiring of protein-protein interactions and signal transduction pathways. Additionally, these studies have driven efforts to systematically map sequence spaces and probe the selective pressures and constraints that govern the evolution of protein-protein interactions.