Abca1

ATP-binding cassette (ABC) transporters are a superfamily of evolutionary conserved membrane proteins that transport a wide variety of substrates, including ions, amino acids, peptides, sugars, lipids, and sterols, across cell membranes. Functional ABC transporters are characterized by a symmetrical structure of four domains: two nucleotide binding domains (NBDs), with diagnostic Walker A, B, and C motifs, and two transmembrane domains (TMDs), each composed of at least 6 transmembrane segments (TMs). On the basis of sequence homology and domain organization, mammalian ABC genes have been classified into seven distinct subfamilies, from ABC-A to ABC-G. While in yeast ABC genes sharing the features of the subfamilies B to G can be identified, ABC genes belonging to the A subfamily have not been detected. The ABCA subfamily is composed of 12 full-size transporters encoded by a single gene. Three of them, ABCA4, ABCA1, and ABCA3, are implicated in genetic disorders, including Stargardt or Tangier disease and fatal surfactant deficiency in newborns, respectively. ABCA1 has been originally identified as an engulfment receptor on macrophages, required for efficient clearance of dying cells. In addition to this scavenging function, ABCA1 plays a major role in cholesterol metabolism. Indeed, it controls the first steps of reverse transport of cholesterol promoting the efflux of cellular cholesterol to plasma apolipoproteins, the core of nascent high density lipoproteins (HDLs). In spite of their physiological relevance, both of these processes are far from being understood in molecular terms. They are, however, both highly dependent from the physicochemical characteristics of the cell membrane, and it is in this context that the function of ABCA1 appears crucial.