ABC Transporters Constitute the Largest Family of Membrane Transport Proteins
The last type of transport ATPase that we discuss is the family of the ABC transporters, so named because each member contains two highly conserved ATPase domains, or ATP-Binding “Cassettes,” on the cytosolic side of the membrane. ATP binding brings together the two ATPase domains, and ATP hydrolysis leads to their dissociation (Figure 11–16). These movements of the cytosolic domains are transmitted to the transmembrane segments, driving cycles of conformational changes that alternately expose solute-binding sites on one side of the membrane and then on the other, as we have seen for other transporters. In this way, ABC transporters harvest the energy released upon ATP binding and hydrolysis to drive transport of solutes across the bilayer. The transport is directional toward inside or toward outside, depending on the particular conformational change in the solute binding site that is linked to ATP hydrolysis (see Figure 11–16).
ABC transporters constitute the largest family of membrane transport proteins and are of great clinical importance. The first of these proteins to be characterized was found in bacteria. We have already mentioned that the plasma membranes of all bacteria contain transporters that use the H+ gradient across the membrane to actively transport a variety of nutrients into the cell. In addition, bacteria use ABC transporters to import certain small molecules. In bacteria such as E. coli that have double membranes (Figure 11–17), the ABC transporters are located in the inner membrane, and an auxiliary mechanism operates to capture the nutrients and deliver them to the transporters (Figure 11–18).
In E. coli, 78 genes (an amazing 5% of the bacterium’s genes) encode ABC transporters, and animal genomes encode an even larger number. Although each transporter is thought to be specific for a particular molecule or class of molecules, the variety of substrates transported by this superfamily is great and includes inorganic ions, amino acids, monoand polysaccharides, peptides, lipids, drugs, and, in some cases, even proteins that can be larger than the transporter itself.
Figure 11–16 Small-molecule transport by typical abC transporters. ABC transporters consist of multiple domains. Typically, two hydrophobic domains, each built of six membrane-spanning α helices, together form the translocation pathway and provide substrate specificity. Two ATPase domains protrude into the cytosol. In some cases, the two halves of the transporter are formed by a single polypeptide, whereas in other cases they are formed by two or more separate polypeptides that assemble into a similar structure. Without ATP bound, the transporter exposes a substrate-binding site on one side of the membrane. ATP binding induces a conformational change that exposes the substrate-binding site on the opposite side; ATP hydrolysis followed by ADP dissociation returns the transporter to its original conformation. Most individual ABC transporters are unidirectional. (A) Both importing and exporting ABC transporters are found in bacteria; an ABC importer is shown in this cartoon. The crystal structure of a bacterial ABC transporter is shown in Figure 3–76.
(B) In eukaryotes, most ABC transporters export substances—either from the cytosol to the extracellular space or from the cytosol to a membrane-bound intracellular compartment such as the endoplasmic reticulum—or from the mitochondrial matrix to the cytosol.