title: Symmetry and structure in P-glycoprotein and ABC transporters what goes around comes around.
abstract: The ABC superfamily of membrane transporters is one of the largest classes of proteins across all species and one of the most intensely researched. ABC proteins are involved in the trafficking of a diverse variety of biological molecules across cell membranes, with some members implicated in medical syndromes such as cystic fibrosis and multidrug resistance to anti-cancer drugs. In the absence of X-ray crystallographic data, structural information has come from spectroscopy, electron microscopy, secondary structure prediction algorithms and residue substitution, epitope labelling and cysteine cross-linking studies. These have generally supported a model for the topology of the transmembrane domains of ABC transporters in which a single aqueous pore is formed by a toroidal ring of 12 alpha helices, deployed in two arcs of six helices each. Although this so-called 6 + 6 helix model can be arranged in either mirror or rotational symmetry configurations, experimental data supports the former. In this review, we put forward arguments against both configurations of this 6 + 6 helix model, based on what is known generally about symmetry relationships in proteins. We relate these arguments to P-glycoprotein, in particular, and discuss alternative models for the structure of ABC transporters in the light of the most recent research.
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Science, University of Technology Sydney, NSW, Australia.
authors.forename: P M
authors.initials: PM
authors.lastname: Jones
authors.forename: A M
authors.initials: AM
authors.lastname: George
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry*; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry*; D000818:Animals; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters