Structure and Molecular Mechanism of a Nucleobase-Cation-Symport-1 Family Transporter

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 outwardand 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.