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
  • Mirza, Osman Asghar
  • 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