The FepA protein is a more complex example of a β barrel transport protein (Figure 10–23D). It transports iron ions across the bacterial outer membrane. It is constructed from 22 β strands, and a large globular domain completely fills the inside of the barrel. Iron ions bind to this domain, which by an unknown mechanism moves or changes its conformation to transfer the iron across the membrane.
Not all β-barrel proteins are transport proteins. Some form smaller barrels that are completely filled by amino acid side chains that project into the center of the barrel. These proteins function as receptors or enzymes (Figure 10–23A and B); the barrel serves as a rigid anchor, which holds the protein in the membrane and orients the cytosolic loops that form binding sites for specific intracellular molecules.
Most multipass membrane proteins in eukaryotic cells and in the bacterial plasma membrane are constructed from transmembrane α helices. The helices
Figure 10–22 Steps in the folding of a multipass transmembrane protein.
When a newly synthesized transmembrane α helix is released into the lipid bilayer, it is initially surrounded by lipid molecules. As the protein folds, contacts between the helices displace some of the lipid molecules surrounding the helices.
Figure 10–23 β barrels formed from different numbers of β strands.
(A) the E. coli OmpA protein serves as a receptor for a bacterial virus. (B) the E. coli OMplA protein is an enzyme (a lipase) that hydrolyzes lipid molecules. the amino acids that catalyze the enzymatic reaction (shown in red) protrude from the outside surface of the barrel. (c) A porin from the bacterium Rhodobacter capsulatus forms a water-filled pore across the outer membrane. the diameter of the channel is restricted by loops (shown in blue) that protrude into the channel. (D) the E. coli FepA protein transports iron ions. the inside of the barrel is completely filled by a globular protein domain (shown in blue) that contains an iron-binding site (not shown).
Figure 10–24 a single-pass transmembrane protein. note that the polypeptide chain traverses the lipid bilayer as a right-handed α helix and that the oligosaccharide chains and disulfide bonds are all on the noncytosolic surface of the membrane. the sulfhydryl groups in the cytosolic domain of the protein do not normally form disulfide bonds because the reducing environment in the cytosol maintains these groups in their reduced (–Sh) form.
can slide against each other, allowing conformational changes in the protein that can open and shut ion channels, transport solutes, or transduce extracellular signals into intracellular ones. In β-barrel proteins, by contrast, hydrogen bonds bind each β strand rigidly to its neighbors, making conformational changes within the wall of the barrel unlikely.
Most transmembrane proteins in animal cells are glycosylated. As in glycolipids, the sugar residues are added in the lumen of the ER and the Golgi apparatus (discussed in Chapters 12 and 13). For this reason, the oligosaccharide chains are always present on the noncytosolic side of the membrane. Another important difference between proteins (or parts of proteins) on the two sides of the membrane results from the reducing environment of the cytosol. This environment decreases the likelihood that intrachain or interchain disulfide (S–S) bonds will form between cysteines on the cytosolic side of membranes. These bonds form on the noncytosolic side, where they can help stabilize either the folded structure of the polypeptide chain or its association with other polypeptide chains (Figure 10–24).