Progress and prospects for structural studies of transmembrane interactions in single-spanning receptors

Single-spanning receptors are typically active in dimeric or oligomeric forms in which ligand-induced complex formation and/or conformational changes are the key events that transmit information across the cell membrane. This process is often depicted exclusively in terms of extracellular receptor-ligand interactions and their intracellular consequences, but the lipid embedded alpha-helical transmembrane domains can also engage in specific intermolecular interactions that play important roles in establishing receptor complex structure and regulating signal propagation through the lipid bilayer. Obtaining high-resolution structural information on these interactions is extremely challenging, and the small number of structures currently available in the protein data bank represents only about a dozen unique receptors. In this review, we highlight new structures that provide novel insights into receptor tyrosine kinase and death receptor function and discuss the implications of recent successes in the application of X-ray crystallographic techniques to determine the structures of receptor transmembrane complexes in lipid bilayers.