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Published Online July 3, 2008
Science DOI: 10.1126/science.1160406

Research Articles

Submitted on May 13, 2008
Accepted on June 18, 2008

The Crystal Structure of a Sodium Galactose Transporter Reveals Mechanistic Insights into Na+/Sugar Symport

Salem Faham 1, Akira Watanabe 1, Gabriel Mercado Besserer 1, Duilio Cascio 2, Alexandre Specht 3, Bruce A. Hirayama 1, Ernest M. Wright 1*, Jeff Abramson 1*

1 Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095–1751, USA.
2 UCLA-Department of Energy Institute of Genomics and Proteomics, University of California, Los Angeles, CA 90095, USA.
3 Laboratoire de Chimie Bioorganique, Université Louis Pasteur / CNRS UMR 7175 LC01, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch, France.

* To whom correspondence should be addressed.
Ernest M. Wright , E-mail: ewright{at}mednet.ucla.edu
Jeff Abramson , E-mail: jabramson{at}mednet.ucla.edu

Membrane transporters that use energy stored in sodium gradients to drive nutrients into cells constitute a major class of proteins. We report the crystal structure of a member of the solute sodium symporters (SSS), the Vibrio parahaemolyticus sodium/galactose symporter (vSGLT). The ~3.0 angstrom structure contains 14 transmembrane (TM) helices in an inward-facing conformation with a core structure of inverted repeats of 5 TM helices (TM2-TM6 and TM7-TM11). Galactose is bound in the center of the core, occluded from the outside solutions by hydrophobic residues. Surprisingly, the architecture of the core is similar to the leucine transporter (LeuT) from a different gene family. Modeling the outward-facing conformation based on the LeuT structure, in conjunction with biophysical data, provides insight into structural rearrangements for active transport.


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