Key Concepts of Section 11.3

• 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).