Assistant: Priscilla Boon
Professor Chan and his research group work on the structure and function of membrane proteins, particularly those that participate in the transport of electrons, ions, sugars, and other substrates that are essential to the life of a cell across the cell membrane. They study these enzymes in the native environment of the membrane in which they reside, or isolate and purify them for in-depth structural and functional characterization by a variety of physical and chemical methods, including NMR, EPR, ENDOR, resonance RAMAN, X-ray spectroscopy, time-resolved absorption and fluorescence spectroscopy, chemical modification, and site-directed mutagenesis. At the moment they are investigating a number of interesting and important systems: cytochrome bo3 from E. coli; cytochrome bc1 oxidase from bovine heart; succinate-ubiquinone oxidoreductase from Paracoccus denitrificans; and the particulate methane monooxygenase from methanotrophic bacteria.
In this work, the laboratory is developing approaches to map the secondary structure and the tertiary folding of the proteins in the lipid bilayer membrane and attempting to understand their protein architecture and the protein dynamics in terms of the primary sequence, and subunit structure, as well as the manner in which proteins interact with the lipids. Many membrane proteins are molecular machines, with mobile elements that are essential to their functions. Accordingly, they are also developing methods to follow these protein conformational changes in real time so that the catalytic chemistry may be understood in terms of the protein design and architecture. It is through these studies that they hope to obtain an understanding of the principles underlying ion and electron transport across biological membranes; the mechanisms of coupled-solute transport mediated by membrane-bound redox-enzymes and transport proteins, especially proton and ion pumps; and biological energy transduction in general.
Finally, in quite a distinct project, the Chan laboratory is developing a new paradigm of protein folding based on the principles of kinetic channeling. Toward testing some of these ideas, experiments are currently underway to observe the early events of protein folding in a number of protein systems.