Secondary active transporters couple transport of substrate to an ion gradient. Transport is proposed to occur through an alternating access mechanism in which a substrate binding site located toward the center of the protein has alternating access to either side of the membrane. Structures of two secondary transporters, the leucine transport protein LeuT and the galactose transport protein vSGLT, are available, but in both structures the substrate is occluded from both sides of the membrane. Now Weyand et al. report outward-facing open and substrate-bound occluded conformations for a nucleobase transporter. Comparison of the outward-facing conformations with the inward-facing substrate-occluded conformation of vSGLT suggests a structural model for how alternate opening and closing of inward- and outward-facing cavities is achieved.
S. Weyand, T. Shimamura, S. Yajima, S. Suzuki, O. Mirza, K. Krusong, E. P. Carpenter, N. G. Rutherford, J. M. Hadden, J. O'Reilly, P. Ma, M. Saidijam, S. G. Patching, R. J. Hope, H. T. Norbertczak, P. C. J. Roach, S. Iwata, P. J. F. Henderson, A. D. Cameron, Structure and molecular mechanism of a nucleobase–cation–symport-1 family transporter. Science 322, 709-713 (2008). [Abstract] [Full Text]