In some proteins one finds discrete regions of compact tertiary structure that are separated by stretches of the polypeptide chain in a more flexible arrange ment. These discrete folded units are known as domains, and often they define functional units of the protein. For example, many cell membrane receptors play a role in signal transduction by binding extracellular ligands at the cell surface. In response to ligand binding, the receptor undergoes a structural change that results in macromolecular interactions between the receptor and other proteins within the cell cytosol. These interactions in turn set off a cascade of biochemical events that ultimately lead to some form of cellular response to ligand binding. To function in this capacity, such a receptor requires a minimum of three separate domains: an extracellular ligand binding domain, a transmembrane domain that anchors the protein within the cell membrane, and an intracellular domain that forms the locus for protein—protein interactions. These concepts are schematically illustrated in Figure 3.16.