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Conformational Sampling and Nucleotide-Dependent Transitions of the GroEL Subunit Probed by Unbiased Molecular Dynamics Simulations

GroEL is an ATP dependent molecular chaperone that promotes the folding of a large number of substrate proteins in E. coli. Large-scale conformational transitions occurring during the reaction cycle have been characterized from extensive crystallographic studies. However, the link between the observ...

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Autores principales: Skjaerven, Lars, Grant, Barry, Muga, Arturo, Teigen, Knut, McCammon, J. Andrew, Reuter, Nathalie, Martinez, Aurora
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053311/
https://www.ncbi.nlm.nih.gov/pubmed/21423709
http://dx.doi.org/10.1371/journal.pcbi.1002004
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author Skjaerven, Lars
Grant, Barry
Muga, Arturo
Teigen, Knut
McCammon, J. Andrew
Reuter, Nathalie
Martinez, Aurora
author_facet Skjaerven, Lars
Grant, Barry
Muga, Arturo
Teigen, Knut
McCammon, J. Andrew
Reuter, Nathalie
Martinez, Aurora
author_sort Skjaerven, Lars
collection PubMed
description GroEL is an ATP dependent molecular chaperone that promotes the folding of a large number of substrate proteins in E. coli. Large-scale conformational transitions occurring during the reaction cycle have been characterized from extensive crystallographic studies. However, the link between the observed conformations and the mechanisms involved in the allosteric response to ATP and the nucleotide-driven reaction cycle are not completely established. Here we describe extensive (in total [Image: see text] long) unbiased molecular dynamics (MD) simulations that probe the response of GroEL subunits to ATP binding. We observe nucleotide dependent conformational transitions, and show with multiple 100 ns long simulations that the ligand-induced shift in the conformational populations are intrinsically coded in the structure-dynamics relationship of the protein subunit. Thus, these simulations reveal a stabilization of the equatorial domain upon nucleotide binding and a concomitant “opening” of the subunit, which reaches a conformation close to that observed in the crystal structure of the subunits within the ADP-bound oligomer. Moreover, we identify changes in a set of unique intrasubunit interactions potentially important for the conformational transition.
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spelling pubmed-30533112011-03-18 Conformational Sampling and Nucleotide-Dependent Transitions of the GroEL Subunit Probed by Unbiased Molecular Dynamics Simulations Skjaerven, Lars Grant, Barry Muga, Arturo Teigen, Knut McCammon, J. Andrew Reuter, Nathalie Martinez, Aurora PLoS Comput Biol Research Article GroEL is an ATP dependent molecular chaperone that promotes the folding of a large number of substrate proteins in E. coli. Large-scale conformational transitions occurring during the reaction cycle have been characterized from extensive crystallographic studies. However, the link between the observed conformations and the mechanisms involved in the allosteric response to ATP and the nucleotide-driven reaction cycle are not completely established. Here we describe extensive (in total [Image: see text] long) unbiased molecular dynamics (MD) simulations that probe the response of GroEL subunits to ATP binding. We observe nucleotide dependent conformational transitions, and show with multiple 100 ns long simulations that the ligand-induced shift in the conformational populations are intrinsically coded in the structure-dynamics relationship of the protein subunit. Thus, these simulations reveal a stabilization of the equatorial domain upon nucleotide binding and a concomitant “opening” of the subunit, which reaches a conformation close to that observed in the crystal structure of the subunits within the ADP-bound oligomer. Moreover, we identify changes in a set of unique intrasubunit interactions potentially important for the conformational transition. Public Library of Science 2011-03-10 /pmc/articles/PMC3053311/ /pubmed/21423709 http://dx.doi.org/10.1371/journal.pcbi.1002004 Text en Skjaerven et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Skjaerven, Lars
Grant, Barry
Muga, Arturo
Teigen, Knut
McCammon, J. Andrew
Reuter, Nathalie
Martinez, Aurora
Conformational Sampling and Nucleotide-Dependent Transitions of the GroEL Subunit Probed by Unbiased Molecular Dynamics Simulations
title Conformational Sampling and Nucleotide-Dependent Transitions of the GroEL Subunit Probed by Unbiased Molecular Dynamics Simulations
title_full Conformational Sampling and Nucleotide-Dependent Transitions of the GroEL Subunit Probed by Unbiased Molecular Dynamics Simulations
title_fullStr Conformational Sampling and Nucleotide-Dependent Transitions of the GroEL Subunit Probed by Unbiased Molecular Dynamics Simulations
title_full_unstemmed Conformational Sampling and Nucleotide-Dependent Transitions of the GroEL Subunit Probed by Unbiased Molecular Dynamics Simulations
title_short Conformational Sampling and Nucleotide-Dependent Transitions of the GroEL Subunit Probed by Unbiased Molecular Dynamics Simulations
title_sort conformational sampling and nucleotide-dependent transitions of the groel subunit probed by unbiased molecular dynamics simulations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053311/
https://www.ncbi.nlm.nih.gov/pubmed/21423709
http://dx.doi.org/10.1371/journal.pcbi.1002004
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