Figure 10–17 shows the different ways in which proteins can associate with the membrane. Like their lipid neighbors, membrane proteins are amphiphilic, having hydrophobic and hydrophilic regions. Many membrane proteins extend through the lipid bilayer, and hence are called transmembrane proteins, with part of their mass on either side (Figure 10–17, examples 1, 2, and 3). Their hydrophobic regions pass through the membrane and interact with the hydrophobic tails of the lipid molecules in the interior of the bilayer, where they are sequestered away from water. Their hydrophilic regions are exposed to water on either side of the membrane. The covalent attachment of a fatty acid chain that inserts into the cytosolic monolayer of the lipid bilayer increases the hydrophobicity of some of these transmembrane proteins (see Figure 10–17, example 1).
Other membrane proteins are located entirely in the cytosol and are attached to the cytosolic monolayer of the lipid bilayer, either by an amphiphilic α helix exposed on the surface of the protein (Figure 10–17, example 4) or by one or more covalently attached lipid chains (Figure 10–17, example 5). Yet other membrane proteins are entirely exposed at the external cell surface, being attached to the lipid bilayer only by a covalent linkage (via a specific oligosaccharide) to a lipid anchor in the outer monolayer of the plasma membrane (Figure 10–17, example 6).
The lipid-linked proteins in example 5 in Figure 10–17 are made as soluble proteins in the cytosol and are subsequently anchored to the membrane by the covalent attachment of the lipid group. The proteins in example 6, however, are made as single-pass membrane proteins in the endoplasmic reticulum (ER). While still in the ER, the transmembrane segment of the protein is cleaved off and a glycosylphosphatidylinositol (GPI) anchor is added, leaving the protein bound to the noncytosolic surface of the ER membrane solely by this anchor (discussed in Chapter 12); transport vesicles eventually deliver the protein to the plasma membrane (discussed in Chapter 13).
By contrast to these examples, membrane-associated proteins do not extend into the hydrophobic interior of the lipid bilayer at all; they are instead bound to either face of the membrane by noncovalent interactions with other membrane proteins (Figure 10–17, examples 7 and 8). Many of the proteins of this type can be released from the membrane by relatively gentle extraction procedures, such as exposure to solutions of very high or low ionic strength or of extreme pH, which interfere with protein–protein interactions but leave the lipid bilayer intact; these proteins are often referred to as peripheral membrane proteins. Transmembrane proteins and many proteins held in the bilayer by lipid groups or hydrophobic polypeptide regions that insert into the hydrophobic core of the lipid bilayer cannot be released in these ways.
lipid Anchors control the Membrane localization of Some Signaling proteins
How a membrane protein is associated with the lipid bilayer reflects the function of the protein. Only transmembrane proteins can function on both sides of
Figure 10–17 Various ways in which proteins associate with the lipid bilayer.
Most membrane proteins are thought to extend across the bilayer as (1) a single α helix, (2) as multiple α helices, or (3) as a rolled-up β sheet (a β barrel). Some of these “single-pass” and “multipass” proteins have a covalently attached fatty acid chain inserted in the cytosolic lipid monolayer (1). Other membrane proteins are exposed at only one side of the membrane. (4) Some of these are anchored to the cytosolic surface by an amphiphilic α helix that partitions into the cytosolic monolayer of the lipid bilayer through the hydrophobic face of the helix.