Four classes of transmembrane proteins couple the energy-releasing hydrolysis of ATP with the energy-requiring transport of substances against their concentration gradients: P-, V-, and F-class pumps and ABC proteins (see Figure 11-9).
The combined action of P-class Na+/K+ ATPases in the plasma membrane and homologous Ca2+ ATPases in the plasma membrane or sarcoplasmic reticulum creates the usual ionic milieu of animal cells: high K+, low Ca2+, and low Na+ in the cytosol; low K+, high Ca2+, and high Na+ in the extracellular fluid.
In P-class pumps, phosphorylation of the α (catalytic) subunit and changes in conformational states are essential for coupling ATP hydrolysis to transport of H+, Na+, K+, or Ca2+ ions (see Figures 11-10 through 11-13).
V- and F-class ATPases, which transport protons exclusively, are large, multisubunit complexes with a proton-conducting channel in the transmembrane domain and ATP-binding sites in the cytosolic domain.
V-class proton pumps in animal lysosomal and endosomal membranes and plant vacuolar membranes are responsible for maintaining a lower pH inside the organelles than in the surrounding cytosol (see Figure 11-14).
All members of the large and diverse ABC superfamily of membrane transport proteins contain four core domains: two transmembrane domains, which form a pathway for solute movement and determine substrate specificity, and two cytosolic ATP-binding domains (see Figure 11-15).
The two T domains of the multidrug transporter ABCB1 form a ligand-binding site in the middle of the plane of the membrane; ligands can bind directly from the cytosol or from the inner membrane leaflet through a gap in the protein.
The ABC superfamily includes about 50 mammalian proteins (e.g., ABCB1, ABCA1) that transport a wide array of substrates, including toxins, drugs, phospholipids, peptides, and proteins, into or out of the cell.
Biochemical experiments directly demonstrate that ABCB4 (MDR2) possesses phospholipid flippase activity (see Figure 11-16).
CFTR, an ABC protein, is a Cl− channel, not a pump. Channel opening is triggered by protein phosphorylation and by binding of ATP to the two A domains (see Figure 11-17).