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

Journal Article · Mon Jan 01 04:00:00 EST 2007 · Nature

DOI:https://doi.org/10.1038/nature05455· OSTI ID:929858

Boudker, O; Ryan, R; Yernool, D; Shimamoto, K; Gouaux, E

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 929858
• Report Number(s): BNL--80424-2008-JA
• Journal Information: Nature, Journal Name: Nature Vol. 445
• Country of Publication: United States
• Language: English

Related Subjects

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