Kinetic mechanism of coupled binding in sodium-aspartate symporter GltPh
Abstract
Many secondary active membrane transporters pump substrates against concentration gradients by coupling their uptake to symport of sodium ions. Symport requires the substrate and ions to be always transported together. Cooperative binding of the solutes is a key mechanism contributing to coupled transport in the sodium and aspartate symporter from Pyrococcus horikoshii GltPh. Here, we describe the kinetic mechanism of coupled binding for GltPh in the inward facing state. The first of the three coupled sodium ions, binds weakly and slowly, enabling the protein to accept the rest of the ions and the substrate. The last ion binds tightly, but is in rapid equilibrium with solution. Its release is required for the complex disassembly. Thus, the first ion serves to 'open the door' for the substrate, the last ion 'locks the door' once the substrate is in, and one ion contributes to both events.
Data availability
Diffraction data have been deposited in PDB under the accession code 6CTF
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Olga Boudker
National Institute of Neurological Disorders and Stroke (R01NS064357)
- Olga Boudker
National Institute of Neurological Disorders and Stroke (R37NS085318)
- Olga Boudker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- José D Faraldo-Gómez, National Heart, Lung and Blood Institute, National Institutes of Health, United States
Version history
- Received: April 5, 2018
- Accepted: September 25, 2018
- Accepted Manuscript published: September 26, 2018 (version 1)
- Version of Record published: October 8, 2018 (version 2)
Copyright
© 2018, Oh & Boudker
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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