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Title: Coupling Substrate and Ion Binding to Extracellular Gate of a Sodium-Dependent Aspartate Transporter

Abstract

Secondary transporters are integral membrane proteins that catalyze the movement of substrate molecules across the lipid bilayer by coupling substrate transport to one or more ion gradients, thereby providing a mechanism for the concentrative uptake of substrates. Here we describe crystallographic and thermodynamic studies of Glt{sub Ph}, a sodium (Na{sup +})-coupled aspartate transporter, defining sites for aspartate, two sodium ions and D,L-threo-{beta}-benzyloxyaspartate, an inhibitor. We further show that helical hairpin 2 is the extracellular gate that controls access of substrate and ions to the internal binding sites. At least two sodium ions bind in close proximity to the substrate and these sodium-binding sites, together with the sodium-binding sites in another sodium-coupled transporter, LeuT, define an unwound {alpha}-helix as the central element of the ion-binding motif, a motif well suited to the binding of sodium and to participation in conformational changes that accompany ion binding and unbinding during the transport cycle.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
929858
Report Number(s):
BNL-80424-2008-JA
TRN: US0806660
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
Nature
Additional Journal Information:
Journal Volume: 445
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 74 ATOMIC AND MOLECULAR PHYSICS; CONFORMATIONAL CHANGES; COUPLING; ELEMENTS; INTEGRALS; IONS; LIPIDS; MEMBRANE PROTEINS; MOLECULES; SODIUM; SODIUM IONS; SUBSTRATES; THERMODYNAMICS; UPTAKE; national synchrotron light source

Citation Formats

Boudker, O, Ryan, R, Yernool, D, Shimamoto, K, and Gouaux, E. Coupling Substrate and Ion Binding to Extracellular Gate of a Sodium-Dependent Aspartate Transporter. United States: N. p., 2007. Web. doi:10.1038/nature05455.
Boudker, O, Ryan, R, Yernool, D, Shimamoto, K, & Gouaux, E. Coupling Substrate and Ion Binding to Extracellular Gate of a Sodium-Dependent Aspartate Transporter. United States. https://doi.org/10.1038/nature05455
Boudker, O, Ryan, R, Yernool, D, Shimamoto, K, and Gouaux, E. 2007. "Coupling Substrate and Ion Binding to Extracellular Gate of a Sodium-Dependent Aspartate Transporter". United States. https://doi.org/10.1038/nature05455.
@article{osti_929858,
title = {Coupling Substrate and Ion Binding to Extracellular Gate of a Sodium-Dependent Aspartate Transporter},
author = {Boudker, O and Ryan, R and Yernool, D and Shimamoto, K and Gouaux, E},
abstractNote = {Secondary transporters are integral membrane proteins that catalyze the movement of substrate molecules across the lipid bilayer by coupling substrate transport to one or more ion gradients, thereby providing a mechanism for the concentrative uptake of substrates. Here we describe crystallographic and thermodynamic studies of Glt{sub Ph}, a sodium (Na{sup +})-coupled aspartate transporter, defining sites for aspartate, two sodium ions and D,L-threo-{beta}-benzyloxyaspartate, an inhibitor. We further show that helical hairpin 2 is the extracellular gate that controls access of substrate and ions to the internal binding sites. At least two sodium ions bind in close proximity to the substrate and these sodium-binding sites, together with the sodium-binding sites in another sodium-coupled transporter, LeuT, define an unwound {alpha}-helix as the central element of the ion-binding motif, a motif well suited to the binding of sodium and to participation in conformational changes that accompany ion binding and unbinding during the transport cycle.},
doi = {10.1038/nature05455},
url = {https://www.osti.gov/biblio/929858}, journal = {Nature},
number = ,
volume = 445,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}