Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter

Research output: Contribution to journalJournal articleResearchpeer-review

Simone Weyand, Tatsuro Shimamura, Shunsuke Yajima, Shun'ichi Suzuki, Osman Asghar Mirza, Kuakarun Krusong, Elisabeth P Carpenter, Nicholas G Rutherford, Jonathan M Hadden, John O'Reilly, Pikyee Ma, Massoud Saidijam, Simon G Patching, Ryan J Hope, Halina T Norbertczak, Peter C J Roach, So Iwata, Peter J F Henderson, Alexander D Cameron

The nucleobase-cation-symport-1 (NCS1) transporters are essential components of salvage pathways for nucleobases and related metabolites. Here, we report the 2.85-angstrom resolution structure of the NCS1 benzyl-hydantoin transporter, Mhp1, from Microbacterium liquefaciens. Mhp1 contains 12 transmembrane helices, 10 of which are arranged in two inverted repeats of five helices. The structures of the outward-facing open and substrate-bound occluded conformations were solved, showing how the outward-facing cavity closes upon binding of substrate. Comparisons with the leucine transporter LeuT(Aa) and the galactose transporter vSGLT reveal that the outward- and inward-facing cavities are symmetrically arranged on opposite sides of the membrane. The reciprocal opening and closing of these cavities is synchronized by the inverted repeat helices 3 and 8, providing the structural basis of the alternating access model for membrane transport.
Original languageEnglish
Issue number5902
Pages (from-to)709-713
Publication statusPublished - 2008

Bibliographical note

Keywords: Actinomycetales; Amino Acid Sequence; Bacterial Proteins; Binding Sites; Cations; Cell Membrane; Crystallography, X-Ray; Hydantoins; Ion Transport; Models, Molecular; Molecular Sequence Data; Nucleobase Transport Proteins; Protein Conformation; Protein Structure, Secondary; Sodium; Symporters

ID: 10488112