2XQ2

Structure of the K294A mutant of vSGLT

Summary for 2XQ2

• Entry DOI: 10.2210/pdb2xq2/pdb
• Related: 3DH4
• Descriptor: SODIUM/GLUCOSE COTRANSPORTER, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• Functional Keywords: transport protein, inverted repeats, leut-fold, galactose, transporter
• Biological source: VIBRIO PARAHAEMOLYTICUS; More
• Cellular location: Cell membrane; Multi-pass membrane protein: P96169 P96169
• Total number of polymer chains: 2
• Total formula weight: 127319.85

Authors

Watanabe, A.,Choe, S.,Chaptal, V.,Rosenberg, J.M.,Wright, E.M.,Grabe, M.,Abramson, J. (deposition date: 2010-09-01, release date: 2010-12-08, Last modification date: 2023-12-20)

Primary citation

Watanabe, A.,Choe, S.,Chaptal, V.,Rosenberg, J.M.,Wright, E.M.,Grabe, M.,Abramson, J.
The Mechanism of Sodium and Substrate Release from the Binding Pocket of Vsglt
Nature, 468:988-, 2010

PubMed Abstract: Membrane co-transport proteins that use a five-helix inverted repeat motif have recently emerged as one of the largest structural classes of secondary active transporters. However, despite many structural advances there is no clear evidence of how ion and substrate transport are coupled. Here we report a comprehensive study of the sodium/galactose transporter from Vibrio parahaemolyticus (vSGLT), consisting of molecular dynamics simulations, biochemical characterization and a new crystal structure of the inward-open conformation at a resolution of 2.7 Å. Our data show that sodium exit causes a reorientation of transmembrane helix 1 that opens an inner gate required for substrate exit, and also triggers minor rigid-body movements in two sets of transmembrane helical bundles. This cascade of events, initiated by sodium release, ensures proper timing of ion and substrate release. Once set in motion, these molecular changes weaken substrate binding to the transporter and allow galactose readily to enter the intracellular space. Additionally, we identify an allosteric pathway between the sodium-binding sites, the unwound portion of transmembrane helix 1 and the substrate-binding site that is essential in the coupling of co-transport.

PubMed: 21131949
DOI: 10.1038/NATURE09580

Experimental method

X-RAY DIFFRACTION (2.73 Å)