TCBG Seminar

Computational experiments reveal signaling mechanisms in membrane proteins: From structural motifs to functional microdomains

Professor Harel Weinstein
Department of Physiology and Biophysics
Mount Sinai School of Medicine
New York, New York

Monday, October 23, 2000
3:00 pm (CT)
3269 Beckman Institute


G protein coupled receptors (GPCRs), among the best studied and functionally most diverse membrane-bound receptor proteins, are responsible for recognizing and transducing the signals of a large variety of intercellular and sensory messengers. GPCRs mediate the actions of neuro-transmitters, hormones, growth and developmental factors, as well as the transduction of sensory signals including light, odorants and taste. These signaling membrane proteins are abundant in mammalian genomes and much of the signaling in mammalian systems uses GPCRs either directly or as one of the elements of complex mechanisms. Mechanistic insights about their properties and functions at a structural atomic level have emerged from a wide variety of experimental studies, often guided by computational modeling and simulation. These developments have made possible the transition of computation efforts from the structural characterization of GPCR systems to the computational analysis of their function. The presentation will illustrate results from interdisciplinary collaborations of computational and experimental studies of mechanisms of signal transduction in GPCRs. The focus will be on the role of receptor structure in ligand-induced transduction of the activation signal in GPCRs, and on the relation of receptor functions and receptor states to structural details and to measurable "responses" and ligand "efficacy". Insights from computational simulations will be shown to identify structural motifs that act as functional microdomains (SM/FMs), providing a structural context for mechanisms of "ligand binding" "constitutive activity", "inverse agonism", and ligand-induced coupling selectivity. A scheme for genome annotation using the SM/FMs in the GPCRs will be illustrated as a step in the construction of a functional genomics approach for these systems.

Tea and coffee will be served in R3151 Beckman Institute at 2:15pm.

Main TCBG Seminars page