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

Research output: Contribution to journalArticle

201 Citations (Scopus)

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
Externally publishedYes

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Hydantoins
Sodium
Membranes
Molecular Dynamics Simulation
Carrier Proteins
Proteins

ASJC Scopus subject areas

  • General

Cite this

Shimamura, T., Weyand, S., Beckstein, O., Rutherford, N. G., Hadden, J. M., Sharpies, D., ... 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

Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1. / Shimamura, Tatsuro; Weyand, Simone; Beckstein, Oliver; Rutherford, Nicholas G.; Hadden, Jonathan M.; Sharpies, David; Sansom, Mark S P; Iwata, So; Henderson, Peter J F; Cameron, Alexander D.

In: Science, Vol. 328, No. 5977, 23.04.2010, p. 470-473.

Research output: Contribution to journalArticle

Shimamura, T, Weyand, S, Beckstein, O, Rutherford, NG, Hadden, JM, Sharpies, D, Sansom, MSP, Iwata, S, Henderson, PJF & Cameron, AD 2010, 'Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1', Science, vol. 328, no. 5977, pp. 470-473. https://doi.org/10.1126/science.1186303
Shimamura, Tatsuro ; Weyand, Simone ; Beckstein, Oliver ; Rutherford, Nicholas G. ; Hadden, Jonathan M. ; Sharpies, David ; Sansom, Mark S P ; Iwata, So ; Henderson, Peter J F ; Cameron, Alexander D. / Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1. In: Science. 2010 ; Vol. 328, No. 5977. pp. 470-473.
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