James U. Bowie, Ph.D.

Research

Membrane proteins comprise roughly a third of all proteins and play crucial biological roles ranging from signal transduction to energy metabolism. Moreover, the vast majority of therapeutic drugs target membrane proteins. In spite of their biological and medical importance, very little is known about how these proteins fold and function. We are attempting to bridge this gap in our knowledge by learning the structures of more membrane proteins, by learning the principles of membrane protein structure stabilization, and by learning how structure relates to function. SAM domains are protein-protein interaction modules found in over 250 regulatory proteins ranging from tyrosine kinase receptors to transcriptional activators and repressor. While all SAM domains adopt a common fold, we have discovered that they display a wide variety of different modes of interaction. This raises interesting evolutionary and biophysical questions concerning the special properties of SAM domains that make them particularly facile protein-protein interactors. With the advent of high throughput structure determination projects, it is becoming increasingly common to for a protein to have a known structure, but unknown function. As a result, an emerging area of study is the prediction of function from structure. To this end, we are studying how unusual surface properties lead to particular functions.