This starter grant award to the University of Colorado at Boulder supports the research of Professor Deborah S. Wuttke. The research focusses on the mechanism by which unstructured polypeptides fold into protein structures. The technique of time-resolved nuclear magnetic resonance spectroscopy is employed for study in real time of the pathways of folding and unfolding in ribonuclease A. Through site-specifically, isotopically labeled residues in the N-terminal region of ribonuclease A, the study takes advantage of the ability of 1D nuclear magnetic resonance spectroscopy to provide information on specific sites in a protein during the course of folding and circumvents the difficulties of assignment and resolution. Each species is well-resolved, allowing the chemical shift and crosspeak lineshapes, as indicators of local structural environment and dynamical properties, to be followed throughout the entire kinetic process. The research is important in the fundamental understanding of protein folding and the mechanism of formation of ribonuclease A, the protein that catalyzes the cleavage of single-stranded ribonucleic acid in the course of life-sustaining genetic processes.
