Biophysical chemistry: Spectroscopic studies of membrane protein folding and dynamics
University of California at Berkeley
Massachusetts Institute of Technology
Massachusetts Institute of Technology
Awards and Academic Honors
N.I.H. Postdoctoral Fellow, California Institute of Technology
Postdoctoral fellow, University of California at Berkeley,
Integral membrane proteins comprise ~30% of all cell proteins, and play essential roles in cellular functions as gates, pumps, receptors, energy transducers, and enzymes. Despite recent progress towards understanding the structure and function of membrane proteins, a more complex and fundamental question persists: What are the molecular mechanisms for the folding, insertion, and assembly of integral membrane proteins that give rise to functional structures?
A broad range of spectroscopic and kinetics studies in our laboratory are aimed towards unveiling the mechanisms of folding, misfolding, and aggregation of ubiquitous bacterial membrane proteins. We aim to elucidate the structural evolution of beta-barrel membrane pores (PDB file 2OMF shown) and alpha-helical membrane proteins as well as changes in their immediate environment during a folding reaction, with special emphasis on: (1) site-specific intra- and intermolecular distances; (2) development of secondary, tertiary, and hydrogen bonding structures; and (3) changes in solvation. An additional critical component is to probe the triggers that induce protein misfolding and aggregation. Tools available in our lab include steady-state and time-resolved resonance emission spectroscopy, correlation spectroscopy, and molecular cell biology and peptide synthesis techniques.
A molecular understanding of membrane protein folding in vitro may provide clues to the complex folding process in vivo and hence, shed light on important topics in health and medicine. Specifically, our studies may elucidate pathogenic pathways of bacterial toxins as well as deepen our understanding of numerous membrane protein misfolding diseases, such as cystic fibrosis and diabetes. Our group's efforts in the study of biomolecules in cell membranes will not only contribute to progress in fundamental research, but will exemplify the exciting progress that can be made by working at the intersection of chemistry, physics, and biology.
Primary Research Area
Research mentoring: I have mentored undergraduate and graduate students in my laboratory. I have also mentored or co-mentored postdoctoral researchers. Of these students and postdocs, 22 are female or underrepresented. I have also participated in campus-wide programs that enhance diversity, including McNair, CAMP Science, Competitive EDGE, and Initiative for Maximizing Student Diversity (IMSD) programs.
Outreach: I continue to present seminars at universities and programs with large underrepresented populations (Cal State LA, Cal State Long Beach, Biophysical Society Summer School at UNC for minority, disadvantaged, and disabled students). I have also participated in the Sally Ride Festival; this program focuses on middle-school girls, and exposes them to the world of science. Other outreach events include hosting a Girl Scout Brownie Troop in “Women in Science” Day, and volunteering in the Greater San Diego Science and Engineering Fair as a judge for the high school section.
Recruiting: I am a regular participant in departmental recruiting for our graduate program. I co-represent our department at graduate school fairs at the Biophysical Society and American Chemical Society Meetings to attract a diverse group of students to our program. My group and I have also hosted and provided lab tours to undergraduates from various colleges, such as Morehouse and Spellman Colleges, College of the Canyons, and colleges from Korea.
- Gable JE, Schlamadinger DE, Cogen AL, Gallo RL, Kim JE, "Fluorescence and UV resonance Raman study of peptide-vesicle interactions of human cathelicidin LL-37 and its F6W and F17W mutants.", Biochemistry, 2009, Vol. 48, Issue 47, 11264-72
- Schlamadinger DE, Gable JE, Kim JE, "Hydrogen bonding and solvent polarity markers in the uv resonance raman spectrum of tryptophan: application to membrane proteins.", J Phys Chem B, 2009, Vol. 113, Issue 44, 14769-78
- Shafaat HS, Leigh BS, Tauber MJ, Kim JE, "Resonance Raman characterization of a stable tryptophan radical in an azurin mutant.", J Phys Chem B, 2009, Vol. 113, Issue 1, 382-8
- Tirrell TF, Paddock ML, Conlan AR, Smoll EJ Jr, Nechushtai R, Jennings PA, Kim JE, "Resonance Raman studies of the (His)(Cys)3 2Fe-2S cluster of MitoNEET: comparison to the (Cys)4 mutant and implications of the effects of pH on the labile metal center.", Biochemistry, 2009, Vol. 48, Issue 22, 4747-52
- Babakhani A, Gorfe AA, Kim JE, McCammon JA, "Thermodynamics of peptide insertion and aggregation in a lipid bilayer.", J Phys Chem B, 2008, Vol. 112, Issue 34, 10528-34
- Sanchez KM, Gable JE, Schlamadinger DE, Kim JE, "Effects of tryptophan microenvironment, soluble domain, and vesicle size on the thermodynamics of membrane protein folding: lessons from the transmembrane protein OmpA.", Biochemistry, 2008, Vol. 47, Issue 48, 12844-52
- Sanchez KM, Neary TJ, Kim JE, "Ultraviolet resonance Raman spectroscopy of folded and unfolded states of an integral membrane protein.", J Phys Chem B, 2008, Vol. 112, Issue 31, 9507-11