Abstract
Band 3 is the predominant polypetide and the purported mediator of anion transport in the human erythrocyte membrane. Against a background of minor and apparently unrelated polypeptides of similar electrophoretic mobility, and despite apparent heterogeneity in its glycosylation, the bulk of band 3 exhibits uniform and characteristic behavior. This integral glycoprotein appears to exist as a noncovalent dimer of two ∼ 93,000‐dalton chains which span the membrane asymmetrically. The protein is hydrophobic in its composition and in its behaviour in aqueous solution and is best solubilized and purified in detergent. It can be cleaved while membrane‐bound into large, topographically defined segments. An integral, outer‐surface, 38,000‐dalton fragment bears most of the band 3 carbohydrate. A 17,000‐dalton, hydrophobic glycopeptide fragment spans the membrane. A ∼ 40,000‐dalton hydrophilic segment represents the cytoplasmic domain. In vitro, glyceraldehyde 3‐P dehydrogenase and aldolase bind reversibly, in a metabolite‐sensitive fashion, to this cytoplasmic segment. The cytoplasmic domain also bears the amino terminus of this polypetide, in contrast to other integral membrane proteins. Recent electron microscopic analysis suggests that the poles of the band 3 molecule can be seen by freezeetching at the two original membrane surfaces, while freeze‐fracture reveals the transmembrane disposition of band 3 dimer particles.
There is strong evidence that band 3 mediates 1:1 anion exchange across the membrane through a conformational cycle while remaining fixed and asymmetrical. Its cytoplasmic pole can be variously perturbed and even excised without a significant alteration of transport function. However, digestion of the outer‐surface region leads to inhibition of transport, so that both this segment and the membrane‐spanning piece (which is slectively labeled by covalent inhibitors of transport) may be presumed to be involved in transport. Genetic polymorphism has been observed in the structure and immunogenicity of the band 3 polypeptide but this feature has not been related to variation in anion transport or other band 3 activities.