(5) Others are attached to the bilayer solely by a covalently bound lipid chain—either a fatty acid chain or a prenyl group (see Figure 10–18)—in the cytosolic monolayer or, (6) via an oligosaccharide linker, to phosphatidylinositol in the noncytosolic monolayer—called a gpI anchor. (7, 8) Finally, membrane-associated proteins are attached to the membrane only by noncovalent interactions with other membrane proteins. the way in which the structure in (5) is formed is illustrated in Figure 10–18, while the way in which the gpI anchor shown in (6) is formed is illustrated in Figure 12–52. the details of how membrane proteins become associated with the lipid bilayer are discussed in chapter 12.
the bilayer or transport molecules across it. Cell-surface receptors, for example, are usually transmembrane proteins that bind signal molecules in the extracellular space and generate different intracellular signals on the opposite side of the plasma membrane. To transfer small hydrophilic molecules across a membrane, a membrane transport protein must provide a path for the molecules to cross the hydrophobic permeability barrier of the lipid bilayer; the molecular architecture of multipass transmembrane proteins (Figure 10–17, examples 2 and 3) is ideally suited for this task, as we discuss in Chapter 11.
Proteins that function on only one side of the lipid bilayer, by contrast, are often associated exclusively with either the lipid monolayer or a protein domain on that side. Some intracellular signaling proteins, for example, that help relay extracellular signals into the cell interior are bound to the cytosolic half of the plasma membrane by one or more covalently attached lipid groups, which can be fatty acid chains or prenyl groups (Figure 10–18). In some cases, myristic acid, a saturated 14-carbon fatty acid, is added to the N-terminal amino group of the protein during its synthesis on a ribosome. All members of the Src family of cytoplasmic protein tyrosine kinases (discussed in Chapter 15) are myristoylated in this way. Membrane attachment through a single lipid anchor is not very strong, however, and a second lipid group is often added to anchor proteins more firmly to a membrane. For most Src kinases, the second lipid modification is the attachment of palmitic acid, a saturated 16-carbon fatty acid, to a cysteine side chain of the protein. This modification occurs in response to an extracellular signal and helps recruit the kinases to the plasma membrane. When the signaling pathway is turned off, the palmitic acid is removed, allowing the kinase to return to the cytosol. Other intracellular signaling proteins, such as the Ras family small GTPases (discussed in Chapter 15), use a combination of prenyl group and palmitic acid attachment to recruit the proteins to the plasma membrane.
Many proteins attach to membranes transiently. Some are classical peripheral membrane proteins that associate with membranes by regulated protein–protein interactions. Others undergo a transition from soluble to membrane protein by a conformational change that exposes a hydrophobic peptide or covalently attached lipid anchor. Many of the small GTPases of the Rab protein family that regulate intracellular membrane traffic (discussed in Chapter 13), for example, switch depending on the nucleotide that is bound to the protein. In their GDP-bound state they are soluble and free in the cytosol, whereas in their GTP-bound state their lipid anchor is exposed and tethers them to membranes. They are