Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter.
Weyand S., Shimamura T., Yajima S., Suzuki S., Mirza O., Krusong K., Carpenter EP., Rutherford NG., Hadden JM., O'Reilly J., Ma P., Saidijam M., Patching SG., Hope RJ., Norbertczak HT., Roach PCJ., Iwata S., Henderson PJF., Cameron AD.
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.