The Statistical Conformation of a Highly Flexible Protein: Small-Angle X-Ray Scattering of S. aureus Protein A

Our laboratory is primarily interested in the mechanisms of protein folding. We use nuclear magnetic resonance (NMR) and other types of spectroscopy to study the solution structure, stability and folding reactions of small protein models. These include monomeric λ repressor, the B domain of protein A (BdpA) and various regulator of G-protein signalling (RGS) domains. Our biophysical studies are used to inform our investigations of the role of folding mechanism in the function of proteins in the cell. For example, a naturally occuring cancer-causing mutation in the RGS domain of axin appears to lower the thermodynamic stability of the domain. We are developing methods to compensate for such destabilizing mutations, thereby restoring normal function to the protein.We are also developing computational models of protein folding as a way to better understand the mechanisms and as a tool in the design of new experiments.