A Physical Chemist's Expedition to Explore the World of Membrane Proteins

Abstract

NMR of base-stacking interactions in nucleic acids in solution, dynamic structure of bilayer membranes, membrane biophysics, metal cofactor structure and function, redox linkage and proton pumping in cytochrome c oxidase, methane hydroxylation by the particulate methane monooxygenase, early kinetic events in protein folding AbstractDespite growing up amid humble surroundings, I ended up receiving an excellent education at the University of California at Berkeley and postdoctoral training at Harvard. My academic career at Caltech was shaped by serendipity, inspirational colleagues, and a stimulating research environment, as well as smart, motivated students and postdocs who were willing to join my search for molecular understanding of complex biological systems. From chemical physics I allowed my research to evolve, beginning with the application of NMR to investigate the base stacking of nucleic acid bases in solution, the dynamic structure of membranes, and culminating with the use of various forms of spectroscopy to elucidate the structure and function of membrane proteins and the early kinetic events in protein folding. The journey was a biased random walk driven by my own intellectual curiosity and instincts and by the pace at which I learned biochemistry from my students and postdocs, my colleagues, and the literature and through osmosis during seminars and scientific meetings.

Structure Determination of Membrane Proteins by Nuclear Magnetic Resonance Spectroscopy

“…For some time, investigators attempted to use sonicated liposomes, which do yield NMR signals from the lipids; however, these results were mired in controversy about the severe curvature affecting the packing of the lipids, and possible effects on associated proteins (14). It is uncertain whether any NMR signals have been detected from helical proteins in lipid bilayers, whether sonicated or not, by solution NMR methods.…”

Proton pumping in cytochrome c oxidase: The coupling between proton and electron gating

“…A redox-linked proton pump is a complex molecular machine (3)(4)(5)(6). First, there must be sufficient redox energy to drive the protons uphill: in the case of cytochrome c oxidase, against the protomotive force that exists across the inner membrane of the mitochrondrion.…”