James J. Chou

James J. Chou

Professor, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
James Chou Photo

Transmembrane Signaling and Transport.

We study the transmembrane and membrane-proximal regions of cell surface proteins, including those of viruses and bacteria. Historically, these regions had occupied a "blind spot" in biology because they are often very hydrophobic, sometimes dynamics, and require lipid bilayer environment to be stable. 

We find that NMR spectroscopy can be used effectively to unveil these blind spots. To this end, we have pushed technological envelope to characterize the structure and dynamics of membrane systems in near membrane environment. Some of the achievements include 1) the physical basis of the intra-membrane assembly of activating immune receptors, 2) the mechanistic role of the TCR/CD3 signaling motif in receptor triggering, and 3) the discovery that receptor membrane anchor can mediate receptor clustering to drive signaling. And more recently, in an ultimate challenge of our lab, we revealed the overall architecture of the membrane region of the HIV-1 envelope spike that provided clues to HIV immunogen design. 

The above projects are still ongoing and expected to generate much more surprises. In addition, we continue to develop NMR tools to drive therapeutic research. Characterizing protein-protein or protein-ligand interaction is an important step in screen-based or guided drug development. As a versatile and non-invasive biophysical tool, solution NMR can be used to identify these molecular interactions and investigate their mechanism. On this front, other ongoing projects in the lab involve streamlining protocols for identifying unknown drug binding sites and for characterizing allosteric drug mechanism. 

 

Selected Publications:

Fu Q, Shaik MM, Cai Y, Ghantous F, Piai A, Peng H, Rits-Volloch S, Liu Z, Harrison SC, Seaman MS, Chen B, and Chou JJ: Structure of the membrane proximal external region of HIV-1 envelope glycoprotein.  PNAS, September 5 (2018).
 
Cao C, Wang S, Cui T, Su XC, Chou JJ: Ion and inhibitor binding of the double-ring ion selectivity filter of the Mitochondrial Calcium Uniporter.  PNAS, 114(14):E2846-E2851 (2017).
 
Dev J, Park D, Fu Q, Chen J, Ha HJ, Ghantous F, Herrmann T, Chang W, Liu Z, Frey G, Seaman MS, Chen B, Chou JJ: Structural Basis for Membrane Anchoring of HIV-1 Envelope Spike.  Science, 353(6295):172-5 (2016). 
 
Fu Q, Fu T, Cruz AC, Sengupta P, Thomas SK, Wang S, Siegel RM, Wu H, Chou JJ: Structural Basis and Functional Role of Intramembrane Trimerization of the Fas/CD95 Death Receptor. Molecular Cell, 61(4):602-13 (2016). 
 
Call ME, Wucherpfennig KW, Chou JJ: The structural basis for intramembrane assembly of an activating immunoreceptor complex. Nature Immunology, 11(11):1023-9 (2010).

Contact Information

Harvard Medical School
Seeley G. Mudd Bldg., Room 109
240 Longwood Avenue
Boston, MA 02115
p: 617 432-2920