Structure, dynamics, and interactions of membrane proteins
Intrinsic membrane proteins serve a number of essential functions in all cells. These functions include substrate transport, signalling, and membrane stabilization to cite a few. Despite their abundance (approximately 1/3 of the human genome), their essential functions in normal physiology, and their involvement in many diseases, relatively little is known about the structures of most membrane proteins. This is due in large part to the fact that the membrane proteins are not generally amenable to structural characterization using classical techniques such as X-ray crystallography and NMR. Our laboratory is involved in the development and application of new spectroscopic approaches to determine the structures of intrinsic membrane proteins including how structural rearrangements modulate their biological functions.
Specifically, we are employing spectroscopic techniques including electron paramagnetic resonance, nuclear magnetic resonance, and fluorescence to characterize the structure, dynamics and interactions of the anion exchange protein in human erythrocytes, the receptor for epidermal growth factor (EGF) in A-431 cells and the 5-HT3 receptor in neurons.
Specific questions currently being addressed include: What are the structures of the transmembrane and cytoplasmic domains of the anion exchange protein? What is the nature and extent of interactions between the cytoplasmic domain of the anion exchange protein and the extensive membrane skeleton and how are these interactions altered in erythrocytes exhibiting abnormal fragility from patients with hemolytic anemias? What are the oligomeric structures of the anion exchange protein and the EGF receptor in their native membranes? What molecular rearrangements occur in the EGF receptor upon EGF binding and how are these changes related temporally to activation of its tyrosine kinase activity? How are the subunits of the 5-HT3 receptor arranged and how does this structure lead to the formation of a ligand-gated ion channel? How do compounds that modeulate the function of the 5-HT3 receptor such as ethanol and anesthetics alter its structure and interactions?