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Unlocking the molecular secrets of sodium-coupled transporters

Nature volume 459, pages 347–355 (2009)Cite this article

Abstract

Transmembrane sodium-ion gradients provide energy that can be harnessed by 'secondary transporters' to drive the translocation of solute molecules into a cell. Decades of study have shown that such sodium-coupled transporters are involved in many physiological processes, making them targets for the treatment of numerous diseases. Within the past year, crystal structures of several sodium-coupled transporters from different families have been reported, showing a remarkable structural conservation between functionally unrelated transporters. These atomic-resolution structures are revealing the mechanism of the sodium-coupled transport of solutes across cellular membranes.

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Figure 1: Architecture of the GltPh fold.
Figure 2: Architecture of the LeuT fold.
Figure 3: Conserved substrate- and ion-binding sites in LeuT, vSGLT and Mhp1.
Figure 4: Crystal structures of transport intermediates.
Figure 5: Comparative views of substrate-bound LeuT in the TMSout state (left) and vSGLT in the TMSin state (right).
Figure 6: Transition between outward-facing and inward-facing states in LeuT-fold transporters.

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Acknowledgements

This work was supported by the US National Institutes of Health. E.G. is an investigator with the Howard Hughes Medical Institute. We thank R. Hibbs, K. Hollenstein, H. Owen, S. Singh and A. Sobolevsky for helpful comments and L. Vaskalis for assistance with the figures.

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Authors and Affiliations

  1. Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Oregon, 97239, USA

    Harini Krishnamurthy, Chayne L. Piscitelli & Eric Gouaux

  2. Department of Biochemistry and Molecular Biology Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Oregon, 97239, USA

    Chayne L. Piscitelli

  3. Howard Hughes Medical Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Oregon, 97239, USA

    Eric Gouaux

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Correspondence should be addressed to E.G. (gouauxe@ohsu.edu).

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Krishnamurthy, H., Piscitelli, C. & Gouaux, E. Unlocking the molecular secrets of sodium-coupled transporters. Nature 459, 347–355 (2009). https://doi.org/10.1038/nature08143

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