James J. Chou

Department of BCMP
Harvard Medical School
Seeley G. Mudd Building, Room 109
250 Longwood Ave.
Boston, MA 02115
Tel: (617) 432-2920
Fax: (617) 432-2921
Email: james_chou@hms.harvard.edu

Web Page: http://chou.med.harvard.edu

The long-term broad interest is in understanding the molecular mechanism of membrane-embedded proteins including ion channels, receptors, and transporters. The main biophysical tool we use to study these systems is solution NMR spectroscopy because many small- to medium-sized helical membrane proteins (< 30 kDa) resist crystallization. Our immediate challenge was to push the envelope of NMR to enable structure determination of alpha helical membrane proteins, not only by developing and testing new methods but also by applying them to answer important questions in biology.

Currently, my lab has two major aspects of research. One aspect is the mechanism of proton channels from Influenza viruses. There is a wealth of crystal structures of K+, Cl-, Ca2+, and Mg2+ channels to help us understand how these channels work. However, until very recently, little or no structural information is available for a proton selective pore. We aim to understand how does a proton-conducting channel work in general, and in particular, how do mutations in the Influenza proton channels lead to drug resistant virus strains. The second research focus is on understanding how is T cell receptor (TCR) complex assembled in membrane and how are TCR signals sent across the membrane. The above fundamental questions have all been long standing due to the technical limitation of obtaining high resolution view of the dynamic structural elements that are embedded in the membrane.

In addition to discovering how things work in cellular membrane, which is where my passion truly lies, I recognize the importance of advancing technology in making these discoveries possible. Therefore, my lab also has a large component in developing new spectroscopic techniques and sample preparation protocols to enable NMR studies of membrane proteins of greater complexity

References:

• Oxenoid, K., Chou, J. J.: The structure of phospholamban pentamer reveals a channel-like architecture in membranes. Proc. Natl. Acad. Sci., 102, 10870-10875 (2005).
• Schnell, J. R., Chou, J. J.: Structure and mechanism of the M2 proton channel of influenza A virus. Nature, 451(7178), 591-5 (2008).