Dr. Ropson proposes to investigate several members of the intracellular lipid binding protein family (iLBPs) as a model for the study of protein folding. As the model system, these proteins are characterized by divergent sequences, but their native structures are nearly identical. They also exhibit reversible two-state folding at equilibrium, but their folding mechanisms and the energy landscapes appear to be different. The basic premise is that, in their different folding pathways for these proteins, different regions of the sequence and/or structure are responsible for initiating sites or intermediate states for the folding of these divergent proteins. To test the hypothesis, mass spectrometry and/or NMR will be used to measure proton-deuterium exchange of amide protons. These measurements will enable the PI to identify the different initiating sites/intermediate states. Structural and mechanistic elucidations of the folding processes of these proteins will be investigated by NMR and stopped-flow NMR and CD methods. Single-site mutant proteins will be generated and studied for their effects on the transition state in protein folding.
| Ropson, Ira J; Boyer, Joshua A; Schaeffer, Blake A et al. (2009) Comparison of the folding mechanism of highly homologous proteins in the lipid-binding protein family. Proteins 75:799-806 |
| Burns, L L; Ropson, I J (2001) Folding of intracellular retinol and retinoic acid binding proteins. Proteins 43:292-302 |
