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SUNY at Albany
June 19-23, 2001
Mechanisms in Phototransduction: Crystal Structure of RGS9 and Its Complexes with Ga and Phosphodiesterase
Trimeric G proteins function as molecular switches between seven-helix transmembrane receptors and intracellular effectors. In the GDP-bound resting state, the a subunit is tightly associated with a complex of b and g subunits. Upon receptor-mediated exchange of GDP for GTP, the a subunit dissociates from the bg complex and modulates the function of specific downstream effectors. The activated G proteins can be down-regulated by Regulator of G protein Signaling (RGS) proteins. In the visual cascade, the G protein transducin couples rhodopsin to the effector cyclic GMP phosphodiesterase (PDE). We report three independently solved crystal structures of the GTPase activating protein (GAP) RGS9, its binary complex with Ga in the presence of GDP and aluminum fluoride, and its ternary complex with Ga and the g subunit of the effector molecule PDE in the presence of GDP and aluminum fluoride. Together these three structures reveal insights into the mechanisms involved in effector activation, synergistic acceleration of GTP hydrolysis by RGS9 and PDEg, RGS9 specificity, and RGS activity.
Michele A. Kercher (1,2)*, Kevin C. Slep (1,4), Wei He (3), Christopher W. Cowan (3,4), Theodore G. Wensel (3) & Paul B. Sigler (1,2)
Department of Molecular Biophysics and Biochemistry(1), and Howard Hughes Medical Institute(2),