Protein structures from domain packing--a game of twenty questions?

are ubiquitous. Their role in communicating extracellular events across the cell membrane is essential and has not been overlooked by those interested in the processes of signal transduction and by those attracted to manipulating signal pathways for disease therapy. The nature of GPCRs makes them suitable targets for drug therapy for a number of reasons. Depending on the signal pathway and the desired physiological response, they can be activated (agonists) or blocked (antagonists). The ligand binding site is accessible from the extracellular environment, thereby not requiring drugs to be able to enter the cell. Receptor subtype homology enables the development of ligands having a balanced effect by interacting equally with each subtype. In addition, receptor subtype heterology holds promise for the ability to exquisitely tune ligand specificity for particular tissues and particular physiological re-