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A Coupled Equilibrium Shift Mechanism in Calmodulin-Mediated Signal Transduction

We used nuclear magnetic resonance data to determine ensembles of conformations representing the structure and dynamics of calmodulin (CaM) in the calcium-bound state (Ca(2+)-CaM) and in the state bound to myosin light chain kinase (CaM-MLCK). These ensembles reveal that the Ca(2+)-CaM state include...

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Autores principales: Gsponer, Jörg, Christodoulou, John, Cavalli, Andrea, Bui, Jennifer M., Richter, Barbara, Dobson, Christopher M., Vendruscolo, Michele
Formato: Texto
Lenguaje:English
Publicado: Cell Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2428103/
https://www.ncbi.nlm.nih.gov/pubmed/18462678
http://dx.doi.org/10.1016/j.str.2008.02.017
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author Gsponer, Jörg
Christodoulou, John
Cavalli, Andrea
Bui, Jennifer M.
Richter, Barbara
Dobson, Christopher M.
Vendruscolo, Michele
author_facet Gsponer, Jörg
Christodoulou, John
Cavalli, Andrea
Bui, Jennifer M.
Richter, Barbara
Dobson, Christopher M.
Vendruscolo, Michele
author_sort Gsponer, Jörg
collection PubMed
description We used nuclear magnetic resonance data to determine ensembles of conformations representing the structure and dynamics of calmodulin (CaM) in the calcium-bound state (Ca(2+)-CaM) and in the state bound to myosin light chain kinase (CaM-MLCK). These ensembles reveal that the Ca(2+)-CaM state includes a range of structures similar to those present when CaM is bound to MLCK. Detailed analysis of the ensembles demonstrates that correlated motions within the Ca(2+)-CaM state direct the structural fluctuations toward complex-like substates. This phenomenon enables initial ligation of MLCK at the C-terminal domain of CaM and induces a population shift among the substates accessible to the N-terminal domain, thus giving rise to the cooperativity associated with binding. Based on these results and the combination of modern free energy landscape theory with classical allostery models, we suggest that a coupled equilibrium shift mechanism controls the efficient binding of CaM to a wide range of ligands.
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spelling pubmed-24281032008-06-13 A Coupled Equilibrium Shift Mechanism in Calmodulin-Mediated Signal Transduction Gsponer, Jörg Christodoulou, John Cavalli, Andrea Bui, Jennifer M. Richter, Barbara Dobson, Christopher M. Vendruscolo, Michele Structure Article We used nuclear magnetic resonance data to determine ensembles of conformations representing the structure and dynamics of calmodulin (CaM) in the calcium-bound state (Ca(2+)-CaM) and in the state bound to myosin light chain kinase (CaM-MLCK). These ensembles reveal that the Ca(2+)-CaM state includes a range of structures similar to those present when CaM is bound to MLCK. Detailed analysis of the ensembles demonstrates that correlated motions within the Ca(2+)-CaM state direct the structural fluctuations toward complex-like substates. This phenomenon enables initial ligation of MLCK at the C-terminal domain of CaM and induces a population shift among the substates accessible to the N-terminal domain, thus giving rise to the cooperativity associated with binding. Based on these results and the combination of modern free energy landscape theory with classical allostery models, we suggest that a coupled equilibrium shift mechanism controls the efficient binding of CaM to a wide range of ligands. Cell Press 2008-05-07 /pmc/articles/PMC2428103/ /pubmed/18462678 http://dx.doi.org/10.1016/j.str.2008.02.017 Text en © 2008 ELL & Excerpta Medica. https://creativecommons.org/licenses/by/3.0/This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Gsponer, Jörg
Christodoulou, John
Cavalli, Andrea
Bui, Jennifer M.
Richter, Barbara
Dobson, Christopher M.
Vendruscolo, Michele
A Coupled Equilibrium Shift Mechanism in Calmodulin-Mediated Signal Transduction
title A Coupled Equilibrium Shift Mechanism in Calmodulin-Mediated Signal Transduction
title_full A Coupled Equilibrium Shift Mechanism in Calmodulin-Mediated Signal Transduction
title_fullStr A Coupled Equilibrium Shift Mechanism in Calmodulin-Mediated Signal Transduction
title_full_unstemmed A Coupled Equilibrium Shift Mechanism in Calmodulin-Mediated Signal Transduction
title_short A Coupled Equilibrium Shift Mechanism in Calmodulin-Mediated Signal Transduction
title_sort coupled equilibrium shift mechanism in calmodulin-mediated signal transduction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2428103/
https://www.ncbi.nlm.nih.gov/pubmed/18462678
http://dx.doi.org/10.1016/j.str.2008.02.017
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