This proposal requests support for a Keystone Symposia meeting entitled Mechanisms of Transmembrane Signaling, organized by Oliver P. Ernst and U. Benjamin Kaupp, which will be held in Taos, New Mexico from January 23 - 28, 2011. Cellular membranes present natural borders for signal transduction between cells and their environment. Nature developed different strategies to enable signals to cross the membrane barrier. In the last decade, determination of protein structures has contributed significantly to understanding how ion channels and transporters work. A similar development in the GPCR field just started recently. The integration of all of this exciting new knowledge from structural, biophysical and functional work now provides the basis to discuss and decipher common basic molecular mechanisms. The goal of this meeting is to discuss the molecular mechanisms of transmembrane signaling on the basis of three protein classes: G protein-coupled receptors (GPCRs), ion channels, and transporters. Available protein structures together with information from biophysical and functional approaches will provide a framework for exploring similarities and differences in the underlying mechanisms of these important receptors and channels, as well as proteins with dual or modified functions, such as channel rhodopsin. This first Keystone Symposia meeting on Mechanisms of Transmembrane Signaling is unique among meetings that include discussion of GPCRs due to its focus on the mechanism of protein-protein interaction and discussion of photochemical conversion of ligand and related protein conformational changes in rhodopsins and channel rhodopsins. A comparative view will bring researchers from diverse fields together and stimulate further development of transmembrane signaling proteins in drug discovery and fighting disease. This meeting aims to be a catalyst to link the information obtained from structures of proteins in different conformations with the knowledge gained from functional experiments and spectroscopy. PUBLIC HEALTH RELEVANCE: The Keystone Symposia meeting on Mechanisms of Transmembrane Signaling addresses proteins which are ubiquitous in our body, involved in controlling almost all physiological processes, and thus intimately involved in health and a wide variety of diseases. The design of this meeting - comparing and understanding the molecular mechanisms employed by the proteins involved in transmembrane signaling - will advance development of drugs against many diseases.