Membrane proteins can be classified into three categories—integral, lipid-anchored, and peripheral—on the basis of their position with respect to the membrane (see Figure 7-1). Integral membrane proteins, also called transmembrane proteins, span a phospholipid bilayer and comprise three domains. The cytosolic and exoplasmic domains have hydrophilic exterior surfaces that interact with the aqueous environment on the cytosolic and exoplasmic faces of the membrane. These domains resemble segments of other water-soluble proteins in their amino acid composition and structure. In contrast, the membrane-spanning segments usually contain many hydrophobic amino acids whose side chains protrude outward and interact with the hydrophobic hydrocarbon core of the phospholipid bilayer. In all transmembrane proteins examined to date, the membrane-spanning domains consist of one or more α helices or of multiple β strands. We discuss the ribosomal synthesis and post-translational processing of soluble cytosolic proteins in Chapters 5 and 10; the process by which integral membrane proteins are inserted into membranes as part of their synthesis is discussed in Chapter 13.

Lipid-anchored membrane proteins are bound covalently to one or more lipid molecules. The hydrophobic tail of the attached lipid is embedded in one leaflet of the membrane and anchors the protein to the membrane. The polypeptide chain itself does not enter the phospholipid bilayer.

Peripheral membrane proteins do not directly contact the hydrophobic core of the phospholipid bilayer. Instead, they are bound to the membrane either indirectly by interactions with integral or lipid-anchored membrane proteins or directly by interactions with lipid head groups. Peripheral proteins can be bound to either the cytosolic or the exoplasmic face of the plasma membrane. In addition to these proteins, which are closely associated with the bilayer, cytoskeletal filaments can be more loosely associated with the cytosolic face, usually through one or more peripheral adapter proteins. Such associations with the cytoskeleton provide support for various cellular membranes, helping to determine the cell’s shape and mechanical properties, and play a role in the two-way communication between the cell interior and the exterior, as we learn in Chapter 17. Finally, peripheral proteins on the outer surface of the plasma membrane and the exoplasmic domains of integral membrane proteins are often attached to components of the extracellular matrix or to the cell walls surrounding bacterial and plant cells, providing a crucial interface between the cell and its environment.

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