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Atomic-level characterization of transport cycle thermodynamics in the glycerol-3-phosphate:phosphate antiporter
Membrane transporters actively translocate their substrate by undergoing large-scale structural transitions between inward- (IF) and outward-facing (OF) states (‘alternating-access' mechanism). Despite extensive structural studies, atomic-level mechanistic details of such structural transitions...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598623/ https://www.ncbi.nlm.nih.gov/pubmed/26417850 http://dx.doi.org/10.1038/ncomms9393 |
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author | Moradi, Mahmoud Enkavi, Giray Tajkhorshid, Emad |
author_facet | Moradi, Mahmoud Enkavi, Giray Tajkhorshid, Emad |
author_sort | Moradi, Mahmoud |
collection | PubMed |
description | Membrane transporters actively translocate their substrate by undergoing large-scale structural transitions between inward- (IF) and outward-facing (OF) states (‘alternating-access' mechanism). Despite extensive structural studies, atomic-level mechanistic details of such structural transitions, and as importantly, their coupling to chemical events supplying the energy, remain amongst the most elusive aspects of the function of these proteins. Here we present a quantitative, atomic-level description of the functional thermodynamic cycle for the glycerol-3-phosphate:phosphate antiporter GlpT by using a novel approach in reconstructing the free energy landscape governing the IF↔OF transition along a cyclic transition pathway involving both apo and substrate-bound states. Our results provide a fully atomic description of the complete transport process, offering a structural model for the alternating-access mechanism and substantiating the close coupling between global structural transitions and local chemical events. |
format | Online Article Text |
id | pubmed-4598623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45986232015-10-21 Atomic-level characterization of transport cycle thermodynamics in the glycerol-3-phosphate:phosphate antiporter Moradi, Mahmoud Enkavi, Giray Tajkhorshid, Emad Nat Commun Article Membrane transporters actively translocate their substrate by undergoing large-scale structural transitions between inward- (IF) and outward-facing (OF) states (‘alternating-access' mechanism). Despite extensive structural studies, atomic-level mechanistic details of such structural transitions, and as importantly, their coupling to chemical events supplying the energy, remain amongst the most elusive aspects of the function of these proteins. Here we present a quantitative, atomic-level description of the functional thermodynamic cycle for the glycerol-3-phosphate:phosphate antiporter GlpT by using a novel approach in reconstructing the free energy landscape governing the IF↔OF transition along a cyclic transition pathway involving both apo and substrate-bound states. Our results provide a fully atomic description of the complete transport process, offering a structural model for the alternating-access mechanism and substantiating the close coupling between global structural transitions and local chemical events. Nature Pub. Group 2015-09-29 /pmc/articles/PMC4598623/ /pubmed/26417850 http://dx.doi.org/10.1038/ncomms9393 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Moradi, Mahmoud Enkavi, Giray Tajkhorshid, Emad Atomic-level characterization of transport cycle thermodynamics in the glycerol-3-phosphate:phosphate antiporter |
title | Atomic-level characterization of transport cycle thermodynamics in the glycerol-3-phosphate:phosphate antiporter |
title_full | Atomic-level characterization of transport cycle thermodynamics in the glycerol-3-phosphate:phosphate antiporter |
title_fullStr | Atomic-level characterization of transport cycle thermodynamics in the glycerol-3-phosphate:phosphate antiporter |
title_full_unstemmed | Atomic-level characterization of transport cycle thermodynamics in the glycerol-3-phosphate:phosphate antiporter |
title_short | Atomic-level characterization of transport cycle thermodynamics in the glycerol-3-phosphate:phosphate antiporter |
title_sort | atomic-level characterization of transport cycle thermodynamics in the glycerol-3-phosphate:phosphate antiporter |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598623/ https://www.ncbi.nlm.nih.gov/pubmed/26417850 http://dx.doi.org/10.1038/ncomms9393 |
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