title: Structural model for 12-helix transporters belonging to the major facilitator superfamily.
abstract: The major facilitator superfamily includes a large collection of evolutionarily related proteins that have been implicated in the transport of a variety of solutes and metabolites across the membranes of organisms ranging from bacteria to humans. We have recently reported the three-dimensional structure, at 6.5 A resolution, of the oxalate transporter, OxlT, a representative member of this superfamily. In the oxalate-bound state, 12 helices surround a central cavity to form a remarkably symmetrical structure that displays a well-defined pseudo twofold axis perpendicular to the plane of the membrane as well as two less pronounced, mutually perpendicular pseudo twofold axes in the plane of the membrane. Here, we combined this structural information with sequence information from other members of this protein family to arrive at models for the arrangement of helices in this superfamily of transport proteins. Our analysis narrows down the number of helix arrangements from about a billion starting possibilities to a single probable model for the relative spatial arrangement for the 12 helices, consistent both with our structural findings and with the majority of previous biochemical studies on members of this superfamily.
authors.affiliation: Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Hirai
authors.forename: Jürgen A W
authors.initials: JA
authors.lastname: Heymann
authors.forename: Peter C
authors.initials: PC
authors.lastname: Maloney
authors.forename: Sriram
authors.initials: S
authors.lastname: Subramaniam
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C099549:OxlT protein, bacteria