FIGURE 12.

Hypothesis regarding the topography of band 3. The ∼120,000 ankyrin molecules (64) bind ∼480,000 of the estimated 1,200,000 band 3 molecules in the human red blood cell as band 3 tetramers. These are located in the ankyrin macromolecular complex, with members of the Rh/RhAG complex, at the head end of spectrin. We assume that a small amount of protein 4.2, at least enough to bind the 17,000 molecules of CD47 (13), is also located in this complex. We show here that protein 4.2 binds to the EF domain of α-spectrin, near the binding site of protein 4.1 on β-spectrin. There are ∼240,000 spectrin dimers (64), ∼240,000 molecules of proteins 4.1, and ∼270,000–300,000 molecules of 4.2 in the red cell. Depending on stoichiometry, protein 4.2 and/or protein 4.1 (7) should bind at least an additional 240,000–480,000 copies of band 3 within the actin junctional complex, presumably as dimers. These linkages along with interactions of the ∼30,000 adducin oligomers with band 3 (8) and connections of proteins 4.1-p55 and glycophorin C (for review, see Ref. 27) create a second attachment site for the membrane skeleton. This leaves 120,000–240,000 band 3 dimers free to diffuse in the lipid bilayer. The membrane skeleton proteins are drawn roughly to size, and protein contacts are indicated where known. The relative positions of many of the proteins within the ankyrin complex and the actin junctional complex are not known, and some of the integral membrane proteins are present in much smaller numbers than band 3 (e.g. CD47), so the ankyrin complex and actin junctional complex must vary in composition. Finally, to show its various interactions, the actin protofilament is drawn perpendicular to the membrane plane, jutting out into the cytoplasm, whereas it actually lies parallel to the membrane. GPA, glycophorin A; GPB, glycophorin B; Ank, ankyrin 1 or ankyrin R.