Biophysics Seminar: Professor James U. Bowie, Department of Chemistry and Biochemistry, University of California, Los Angeles

Protein folding is a fundamental process of life with important implications throughout biology. Elaborate mechanisms exist to regulate and assist folding. Moreover, tens of thousands of mutations have now been associated with diseases and it is thought that most of these mutations affect protein folding and trafficking rather than function. Consequently, there has been an enormous effort over the years to understand how proteins fold. Essentially all of the effort has been directed at soluble proteins, however, and membrane proteins have been largely shunted aside. As a result it has usually only been possible to examine the folding and misfolding of biologically and medically interesting membrane proteins in qualitative terms. Quantitative and mechanistic studies have been restricted to a handful of model membrane proteins, in artificial systems, far from natural conditions. Our goal is to ultimately make folding studies of biologically interesting membrane proteins more routine. I will summarize the state of folding experiments with model membrane proteins like bacteriorhodopsin and then describe single molecule methods we are developing that we hope will allow us to examine the folding of complex human membrane proteins, and the causes of misfolding in disease states.