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

Journal article

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.

Authors: Weyand, S; Shimamura, T; Yajima, S; Suzuki, S; Mirza, O

• Publication status: Published
• Journal: Science (New York, N.Y.)
• Volume: 322
• Issue: 5902
• Pages: 709-713
• Publication date: 2008-10-01
• DOI: 10.1126/science.1164440
• EISSN: 1095-9203
• ISSN: 0036-8075
• Language: English
• Keywords: Amino Acid Sequence; Symporters; Crystallography, X-Ray; Protein Conformation; Sodium; Hydantoins; Binding Sites; Models, Molecular; Protein Structure, Secondary; Bacterial Proteins; Actinomycetales; Nucleobase Transport Proteins; Cell Membrane; Molecular Sequence Data; Ion Transport; Cations