Dr. Ching-Ju Tsai will give a talk on Friday, October, 18th in Seminar room S4 (OSZ) starting 14.00 o´clock on
"GPCR–G protein complexes: What can we learn from their structuress"
Abstract:
One of the largest membrane protein families in eukaryotes are G protein-coupled receptors (GPCRs). GPCRs conduct cellular signaling by activating diverse intracellular transducers, among which the heterotrimeric G proteins are the most prominent. In this presentation, I will describe the structures of the visual GPCR rhodopsin and its signaling complex with G proteins solved by X-ray crystallography (1) and cryo-EM (2). To obtain the crystal structure, a highly engineered G protein α subunit, mini-G protein, was used to form a stable complex for crystallization. For the cryo-EM structure, an antibody FAB fragment was raised to prevent dissociation of the rhodopsin complex with the full G protein heterotrimer. Based on these two structures and comparison with other GPCR–G protein complexes, we could provide new insights in the GPCR–G protein signaling events. In contrast to other GPCRs, rhodopsin adopts the same active conformation with or without G protein, effectively acting like a “binary structural switch” to increase efficiency in the visual system. Our analysis of the well-defined GPCR–G protein interface suggests that the precise position of the carboxyl-terminal “hook-like” element of the G protein relative to the TM7/helix 8 joint of the receptor is a significant determinant in selective G protein activation.