TOPOLOGICAL AND SEGMENTAL PHYLOGENETIC ANALYSES OF THE ANION-EXCHANGER (BAND-3) FAMILY OF TRANSPORTERS

Eleven sequenced anion exchanger (AE; band 3) proteins, including five AE1, four AE2 and two AE3 proteins, comprise the anion exchanger family (AEF) of homologous proteins. Eliminating the rat and rabbit proteins that are nearly identical to the corresponding mouse proteins, seven dissimilar members of this family were selected for study, divided into N-terminal, central and C-terminal segments (designated segments 0, 1 and 2, respectively) and analysed separately for sequence similarity and phylogenetic relatedness. Segments 0 are variable in length and sequence, are essentially lacking in some of the members of the AEF, and are not demonstrably homologous in other members of the family, All segments 1 and 2 are homologous, but they exhibit widely differing degrees of sequence divergence. Segments 2 are highly conserved in all AEF proteins. Segments 1 of the AE2 and AE3 proteins are as conserved as are segments 2, but segments 1 of the AE1 proteins have diverged from each other and from the AE2 and AE3 segments 1 much more than have segments 2 oa these same proteins. The distributions of various types of amino acid residues in the putative transmembrane helical spanners of the seven dissimilar members oi the AEF, based on a modification of the 14-spanner model of Wang et al. (1994) was determined, and this distribution was compared with those of other transmembrane transport proteins; of known structure (bacterial rhodopsins, outer membrane porins of Gram-negative bacteria and bacterial photosynthetic reaction centres). Anion exchangers exhibit a predominance of aromatic residues (F, W, Y) at the ends of the putative spanners sind of aliphatic residues (L, I, V, M) in the centres of these spanners. This feature was also a characteristic of bacteriorhodopsins (of alpha- structure) and of bacterial porins (of beta-structure) but not of photosynthetic reaction centres (of oi-structure). Almost all membrane-embedded charged residues in the AEF proteins occur in odd numbered spanners, a unique characteristic of anion exchangers.