Stephen Sprang ( edit )

 B.S. in Biochemistry from California State University of Los Angeles in 1971
Ph.D. in Biochemistry from the University of Wisconsin, Madison in 1977
Postdoctoral studies with Robert Fletterick at the University of Alberta and the University of California at San Francisco, 1978-1983

We study the structural chemistry of signal transduction, particularly as mediated by heterotrimeric G proteins. Experimental approaches include x-ray crystallography, enzymology and spectroscopy. We also use Molecular Dynamics simulations to better understand the conformational changes that occur in G proteins and their effectors.  The following is a brief summary of ongoing research projects. Names of Lab members are italicized; for more information, see the links to their publications in the narrative below.
What is the mechanism by which GTP hydrolysis is coupled to conformational transitions in G proteins?
It is this chemical process that is linked to the termination of signaling activity. Earlier work in the lab focused on structural studies of relevant conformational states of G protein a subunits in the GTP, GDP•Pi and GDP•AlF4--bound forms of the enzyme. More recent work has focused on structural and mutational analysis of a subunits with interesting catalytic properties and  18O kinetic isotope experiments to characterize the chemical structure of the transition state for GTP hydrolysis in various members of the G protein superfamily. 
How do G proteins regulate effectors - how do effectors regulate G proteins?
When bound to GTP, G proteins regulate the activity of signaling molecules called effectors. Effectors may have reciprocal effects on G proteins, most commonly by accelerating GTP hydrolysis (thereby leading to dissociation of the G protein from its effector). Earlier work addressed the regulation of adenylyl cyclase by Gas,
and more recently, the mechanism by which Ga13 regulates G-protein dependent regulators of cytoskeleton formation. These remarkable effectors activate the small G protein, Rho.  At the same time, these effectors deactivate Ga13, resulting in tightly coupled cycles of G-protein activation and deactivation.
How are Ga proteins activated? How is activation prevented?
 
Just as the signaling activity of G protein a subunits is terminated by GTP hydrolysis, it is initiated by GTP binding. GDP dissociation is the kinetic barrier to this process. Our laboratory has studied the mechanism by which GDP dissociation is inhibited by G protein bg heterodimers,  and by the cytosolic, GoLoco-motif containing protein AGS3,  Efforts are also underway to determine the structure of the cytosolic exchange factor, RIC-8, in complex with various G protein a subunits.  

Structural Biology and Biochemistry: Biological Signal Transduction