Chapter 2 - Membrane Topology of the Human ABC Transporter Proteins

Abstract

ABC proteins in all organisms can be recognized by their conserved motifs within the ATP binding domains. This chapter reviews human proteins that are membrane embedded and fulfill various membrane transport or regulatory functions. It is generally accepted that the minimum functional unit requirement for an ABC transporter is the presence of two transmembrane domains and two ATP-binding cassette (ABC) units. These may be present within one polypeptide chain, or within a membrane-bound homo- or heterodimer of “half transporters”. Computer modeling and laborious biochemical experiments are necessary to elucidate membrane topology, that is, the position and orientation of membrane-spanning segments within the polypeptide chain. The generally applied experimental methods include epitope insertion, localization of glycosylation sites, limited proteolysis, and immunochemical techniques. Several computer-assisted empirical prediction methods are available to generate the hydrophobicity profile for a putative transmembrane protein, but such an analysis may provide only a basis for developing experimental strategies for the elucidation of the actual membrane topology. This chapter summarizes the available data on the membrane topology for various ABC transporters by examining the distinct subfamilies. It discusses predicted topology models and their experimental reinforcement or negation, and assesses the relationship between phylogenetic linkages and the arrangement of membrane topology patterns.