Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1

Tatsuro Shimamura, Simone Weyand, Oliver Beckstein, Nicholas G. Rutherford, Jonathan M. Hadden, David Sharpies, Mark S.P. Sansom, So Iwata, Peter J.F. Henderson, Alexander D. Cameron

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210 Scopus citations

Abstract

The structure of the sodium-benzylhydantoin transport protein Mhp1 from Microbacterium liquefaciens comprises a five-helix inverted repeat, which is widespread among secondary transporters. Here, we report the crystal structure of an inward-facing conformation of Mhp1 at 3.8 angstroms resolution, complementing its previously described structures in outward-facing and occluded states. From analyses of the three structures and molecular dynamics simulations, we propose a mechanism for the transport cycle in Mhp1. Switching from the outward- to the inward-facing state, to effect the inward release of sodium and benzylhydantoin, is primarily achieved by a rigid body movement of transmembrane helices 3, 4, 8, and 9 relative to the rest of the protein. This forms the basis of an alternating access mechanism applicable to many transporters of this emerging superfamily.

Original languageEnglish (US)
Pages (from-to)470-473
Number of pages4
JournalScience
Volume328
Issue number5977
DOIs
StatePublished - Apr 23 2010

ASJC Scopus subject areas

  • General

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    Shimamura, T., Weyand, S., Beckstein, O., Rutherford, N. G., Hadden, J. M., Sharpies, D., Sansom, M. S. P., Iwata, S., Henderson, P. J. F., & Cameron, A. D. (2010). Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1. Science, 328(5977), 470-473. https://doi.org/10.1126/science.1186303