Multidrug ABC transporters from bacteria to man: an emerging hypothesis for the universality of molecular mechanism and function

Abstract

. he ATP-binding cassette (ABC) superfamily of membrane-associated transporters encompasses a diverse group of proteins in a wide variety of organisms and cell types, many of which have been implicated in human diseases. In addition to highly homologous ATP-binding domains, most of these proteins have multiple transmembrane (TM) spanning domains and function as ATP-dependent transportersF z In eukaryotic cells, members of this family include the multidrug transporter, P-glycoprotein (P-gp), the related multidrug resistance-associated protein (mrpl) encoded by the MRP1 gene, 3 the cystic fibrosis transmembrane regulator (CFTR), ~ the STE6 a-mating factor transporter in the yeast Saccbaromyces cerevisiae, 5,6 and the ABCR protein in retina implicated in macular degeneration. 7,8 Additional members of this family are the peroxisomal membrane pumps, PMPTO 9-11 and ALDP ~2 and the related ALDRP I3 whose mutated versions have been implicated in the cerebro-hepato-renal autosomal recessive disorder Zellweger syndrome and PERSPECTIVES