Proteins that reside within cellular membranes are at the heart of many important life processes, including photosynthesis, respiration, and immune responses. For a protein to function properly, it must fold into a specific three-dimensional (3-D) shape or structure. The Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Judy E. Kim from the University of California at San Diego to investigate one of the most important and challenging aspects of membrane proteins, their folding into correct 3-D structures. Incorrectly folded proteins can cause diseases, such as Alzheimer’s and cystic fibrosis. This research study focuses on understanding the folding of a set of membrane proteins (OmpA and OmpT) to better understand how these proteins assemble in bacteria. While establishing the 3-D structures of membrane proteins remains a grand challenge of structural biology, establishing the folding pathways for these and other proteins is especially challenging. One of the most important goals of this research is to better understand how interactions between the membrane protein and its local environment impact folding. State-of-the-art biophysical techniques will be brought to bear on this problem. Undergraduate and graduate students involved with the project are trained to become skilled researchers at the chemistry/biology interface, while building other important career skills such as communication and leadership. An integral part of this project involves outreach to help broaden participation in the sciences. A summer training program, Preparing Undergraduate Researchers for Protein Lab Experiments (PURPLE), will provide basic research skills to early-stage college students from underserved communities in a committed effort to enhance diversity in STEM. This training program and strong translational connections of the research to the biology of living systems make the project well-suited to inspire undergraduates at an early stage to explore scientific research.
This interdisciplinary project focuses on the folding of two beta-barrel integral membrane proteins, OmpA and OmpT. The motivation is to gain a more complete understanding of the dehydration process and the role of a native chaperone protein during the membrane insertion process and the folding of these membrane proteins. The primary tools include steady-state and time-resolved electronic and vibrational spectroscopy that report on details of the protein structure and changes in the local environment during folding. Various targeted protein mutants involving the judicious placement of tryptophan residues will be generated. These tryptophan residues are exploited as spectroscopic reporting chromophores to elucidate specific interactions between these residues and their environment. Results from this project are expected to advance knowledge and understanding in the fields of membrane protein dynamics and folding. Additionally, the biophysical approaches taken here and the experimental findings of these studies may serve to nucleate complementary theoretical and experimental studies of protein dynamics in other complex biological assemblies.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
