THE STRUCTURE AND FUNCTION OF BAND-3 (AE1) - RECENT DEVELOPMENTS (REVIEW)

This review discusses recent advances in our understanding of the stru cture, function and molecular genetics of the membrane domain of red c ell anion exchanger, band 3 (AE1), and its role in red cell and kidney disease. A new model for the topology of band 3 has been proposed, wh ich suggests the membrane domain has 12 membrane spans, rather than th e 14 membrane spans of earlier models. The major difference between th e models is in the topology of the region on the C-terminal side of me mbrane spans 1-7. Two dimensional crystals of the deglycosylated membr ane domain of band 3 have yielded two and three dimensional projection maps of the membrane domain dimer at low resolution. The human band 3 gene has been completely sequenced and this has facilitated the study of natural band 3 mutations and their involvement in disease. About 2 0% of hereditary spherocytosis cases arise from heterozygosity for ban d 3 mutations, and result in the absence or decrease of the mutant pro tein in the red cell membrane. Several other natural band 3 mutations are known that appear to be clinically benign, but alter red cell phen otype or are associated with altered red cell blood group antigens. Th ese include the mutant band 3 present in Southeast Asian ovalocytosis, a condition which provides protection against cerebral malaria in chi ldren. Familial distal renal tubular acidosis, a condition associated with kidney stones, has been shown to result from a novel group of ban d 3 mutations. The total absence of band 3 has been described in anima ls-occurring naturally in cattle and after targeted disruption in mice . Some of these severely anaemic animals survive, so band 3 is not str ictly essential for life. Although the band 3-negative red cells were very unstable, they contained a normally-assembled red cell skeleton, suggesting that the bilayer of the normal red cell membrane is stabili zed by band 3 interactions with membrane lipids, rather than by intera ctions with the spectrin skeleton.