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Application of rate-equilibrium free energy relationship analysis to nonequilibrium ion channel gating mechanisms

Rate-equilibrium free energy relationship (REFER) analysis provides information on transition-state structures and has been applied to reveal the temporal sequence in which the different regions of an ion channel protein move during a closed–open conformational transition. To date, the theory used t...

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Autor principal: Csanády, László
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717696/
https://www.ncbi.nlm.nih.gov/pubmed/19635854
http://dx.doi.org/10.1085/jgp.200910268
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author Csanády, László
author_facet Csanády, László
author_sort Csanády, László
collection PubMed
description Rate-equilibrium free energy relationship (REFER) analysis provides information on transition-state structures and has been applied to reveal the temporal sequence in which the different regions of an ion channel protein move during a closed–open conformational transition. To date, the theory used to interpret REFER relationships has been developed only for equilibrium mechanisms. Gating of most ion channels is an equilibrium process, but recently several ion channels have been identified to have retained nonequilibrium traits in their gating cycles, inherited from transporter-like ancestors. So far it has not been examined to what extent REFER analysis is applicable to such systems. By deriving the REFER relationships for a simple nonequilibrium mechanism, this paper addresses whether an equilibrium mechanism can be distinguished from a nonequilibrium one by the characteristics of their REFER plots, and whether information on the transition-state structures can be obtained from REFER plots for gating mechanisms that are known to be nonequilibrium cycles. The results show that REFER plots do not carry information on the equilibrium nature of the underlying gating mechanism. Both equilibrium and nonequilibrium mechanisms can result in linear or nonlinear REFER plots, and complementarity of REFER slopes for opening and closing transitions is a trivial feature true for any mechanism. Additionally, REFER analysis provides limited information about the transition-state structures for gating schemes that are known to be nonequilibrium cycles.
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spelling pubmed-27176962010-02-01 Application of rate-equilibrium free energy relationship analysis to nonequilibrium ion channel gating mechanisms Csanády, László J Gen Physiol Article Rate-equilibrium free energy relationship (REFER) analysis provides information on transition-state structures and has been applied to reveal the temporal sequence in which the different regions of an ion channel protein move during a closed–open conformational transition. To date, the theory used to interpret REFER relationships has been developed only for equilibrium mechanisms. Gating of most ion channels is an equilibrium process, but recently several ion channels have been identified to have retained nonequilibrium traits in their gating cycles, inherited from transporter-like ancestors. So far it has not been examined to what extent REFER analysis is applicable to such systems. By deriving the REFER relationships for a simple nonequilibrium mechanism, this paper addresses whether an equilibrium mechanism can be distinguished from a nonequilibrium one by the characteristics of their REFER plots, and whether information on the transition-state structures can be obtained from REFER plots for gating mechanisms that are known to be nonequilibrium cycles. The results show that REFER plots do not carry information on the equilibrium nature of the underlying gating mechanism. Both equilibrium and nonequilibrium mechanisms can result in linear or nonlinear REFER plots, and complementarity of REFER slopes for opening and closing transitions is a trivial feature true for any mechanism. Additionally, REFER analysis provides limited information about the transition-state structures for gating schemes that are known to be nonequilibrium cycles. The Rockefeller University Press 2009-08 /pmc/articles/PMC2717696/ /pubmed/19635854 http://dx.doi.org/10.1085/jgp.200910268 Text en © 2009 Csanády This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jgp.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Csanády, László
Application of rate-equilibrium free energy relationship analysis to nonequilibrium ion channel gating mechanisms
title Application of rate-equilibrium free energy relationship analysis to nonequilibrium ion channel gating mechanisms
title_full Application of rate-equilibrium free energy relationship analysis to nonequilibrium ion channel gating mechanisms
title_fullStr Application of rate-equilibrium free energy relationship analysis to nonequilibrium ion channel gating mechanisms
title_full_unstemmed Application of rate-equilibrium free energy relationship analysis to nonequilibrium ion channel gating mechanisms
title_short Application of rate-equilibrium free energy relationship analysis to nonequilibrium ion channel gating mechanisms
title_sort application of rate-equilibrium free energy relationship analysis to nonequilibrium ion channel gating mechanisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717696/
https://www.ncbi.nlm.nih.gov/pubmed/19635854
http://dx.doi.org/10.1085/jgp.200910268
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