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A multi-substrate single-file model for ion-coupled transporters

Su, Alyce and Mager, Sela and Mayo, Stephen L. and Lester, Henry A. (1996) A multi-substrate single-file model for ion-coupled transporters. Biophysical Journal, 70 (2). pp. 762-777. ISSN 0006-3495. http://resolver.caltech.edu/CaltechAUTHORS:20110620-160434844

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Abstract

Ion-coupled transporters are simulated by a model that differs from contemporary alternating-access schemes. Beginning with concepts derived from multi-ion pores, the model assumes that substrates (both inorganic ions and small organic molecules) hop a) between the solutions and binding sites and b) between binding sites within a single-file pore. No two substrates can simultaneously occupy the same site. Rate constants for hopping can be increased both a) when substrates in two sites attract each other into a vacant site between them and b) when substrates in adjacent sites repel each other. Hopping rate constants for charged substrates are also modified by the membrane field. For a three-site model, simulated annealing yields parameters to fit steady-state measurements of flux coupling, transport-associated currents, and charge movements for the GABA transporter GAT1. The model then accounts for some GAT1 kinetic data as well. The model also yields parameters that describe the available data for the rat 5-HT transporter and for the rabbit Na(+)-glucose transporter. The simulations show that coupled fluxes and other aspects of ion transport can be explained by a model that includes local substrate-substrate interactions but no explicit global conformational changes.


Item Type:Article
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URLURL TypeDescription
http://dx.doi.org/10.1016/S0006-3495(96)79616-9DOIUNSPECIFIED
http://www.sciencedirect.com/science/article/pii/S0006349596796169PublisherUNSPECIFIED
Additional Information:© 1996 The Biophysical Society; Published by Elsevier Inc. Received for publication 25 July 1995 and in final form 21 October 1995. Available online 2 January 2009. We thank Eric Bax, Bassil Dahiyat, Norman Davidson, and Jun Li for suggestions. Scott Fraser suggested the diffusion pump analogy. This work was supported by grants from the National Institute of Neurological Diseases and Stroke and the National Institute on Drug Abuse. SLM acknowledges support from the Rita Allen Foundation, the David and Lucille Packard Foundation, and the Searle Scholars Program.
Funders:
Funding AgencyGrant Number
National Institute of Neurological Disease and StrokeUNSPECIFIED
National Institute on Drug AbuseUNSPECIFIED
Rita Allen FoundationUNSPECIFIED
David and Lucille Packard FoundationUNSPECIFIED
Searle Scholars ProgramUNSPECIFIED
Subject Keywords:GABA Plasma Membrane Transport Proteins, Carrier Proteins, Biophysics, Serotonin, Monosaccharide Transport Proteins, Molecular Structure, Ion Transport, Electrochemistry, Nerve Tissue Proteins, Models: Biological, Animals, Serotonin Plasma Membrane Transport Proteins, Membrane Glycoproteins, Binding Sites, Membrane Transport Proteins, Organic Anion Transporters, Membrane Potentials, Membrane Proteins, gamma-Aminobutyric Acid, Computer Simulation, Sodium, Sodium-Glucose Transporter 1, Biophysical Phenomena
Record Number:CaltechAUTHORS:20110620-160434844
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20110620-160434844
Official Citation:A. Su, S. Mager, S.L. Mayo, H.A. Lester, A multi-substrate single-file model for ion-coupled transporters, Biophysical Journal, Volume 70, Issue 2, February 1996, Pages 762-777, ISSN 0006-3495, DOI: 10.1016/S0006-3495(96)79616-9. (http://www.sciencedirect.com/science/article/pii/S0006349596796169)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:24130
Collection:CaltechAUTHORS
Deposited By: Marie Ary
Deposited On:22 Jun 2011 14:47
Last Modified:22 Jun 2011 14:47

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