Membrane proteins are defined by their location within or at the surface of a phospholipid bilayer. Although every biological membrane has the same basic bilayer structure, the proteins associated with a particular membrane are responsible for its distinctive activities. The kinds and amounts of proteins associated with biomembranes vary depending on cell type and subcellular location. For example, the inner mitochondrial membrane is 76 percent protein; the myelin membrane that surrounds nerve axons, only 18 percent. The high phospholipid content of myelin allows it to electrically insulate the nerve from its environment, as we discuss in Chapter 22. The importance of membrane proteins is evident from the finding that approximately a third of all yeast genes encode a membrane protein. The relative abundance of genes for membrane proteins is even greater in multicellular organisms, in which membrane proteins have additional functions in cell adhesion and in communication between different cell types (cell-cell interactions).

The lipid bilayer presents a distinctive two-dimensional hydrophobic environment for membrane proteins. Some proteins contain segments that are embedded within the hydrophobic core of the phospholipid bilayer; other proteins are associated with the exoplasmic or cytosolic leaflet of the bilayer. Protein domains on the extracellular surface of the plasma membrane generally bind to extracellular molecules, including external signaling proteins, ions, and small metabolites (e.g., glucose, fatty acids), as well as proteins on other cells or in the external environment. Segments of proteins within the plasma membrane perform multiple functions, such as forming the channels and pores through which molecules and ions move into and out of cells. These intramembrane segments also serve to organize multiple membrane proteins into larger assemblies within the plane of the membrane. Domains lying along the cytosolic face of the plasma membrane have a wide range of functions, from anchoring cytoskeletal proteins to the membrane to triggering intracellular signaling pathways.

In many cases, the function of a membrane protein and the topology of its polypeptide chain in the membrane can be predicted on the basis of its similarity with other well-characterized proteins. In this section, we examine the characteristic structural features of membrane proteins and some of their basic functions. We describe the structures of several proteins to help you get a feel for the way membrane proteins interact with membranes. More complete characterizations of the properties of various types of membrane proteins are presented in later chapters that focus on their structures and activities in the context of their cellular functions.