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The Effect of Macromolecular Crowding, Ionic Strength and Calcium Binding on Calmodulin Dynamics
The flexibility in the structure of calmodulin (CaM) allows its binding to over 300 target proteins in the cell. To investigate the structure-function relationship of CaM, we combined methods of computer simulation and experiments based on circular dichroism (CD) to investigate the structural charac...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145654/ https://www.ncbi.nlm.nih.gov/pubmed/21829336 http://dx.doi.org/10.1371/journal.pcbi.1002114 |
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author | Wang, Qian Liang, Kao-Chen Czader, Arkadiusz Waxham, M. Neal Cheung, Margaret S. |
author_facet | Wang, Qian Liang, Kao-Chen Czader, Arkadiusz Waxham, M. Neal Cheung, Margaret S. |
author_sort | Wang, Qian |
collection | PubMed |
description | The flexibility in the structure of calmodulin (CaM) allows its binding to over 300 target proteins in the cell. To investigate the structure-function relationship of CaM, we combined methods of computer simulation and experiments based on circular dichroism (CD) to investigate the structural characteristics of CaM that influence its target recognition in crowded cell-like conditions. We developed a unique multiscale solution of charges computed from quantum chemistry, together with protein reconstruction, coarse-grained molecular simulations, and statistical physics, to represent the charge distribution in the transition from apoCaM to holoCaM upon calcium binding. Computationally, we found that increased levels of macromolecular crowding, in addition to calcium binding and ionic strength typical of that found inside cells, can impact the conformation, helicity and the EF hand orientation of CaM. Because EF hand orientation impacts the affinity of calcium binding and the specificity of CaM's target selection, our results may provide unique insight into understanding the promiscuous behavior of calmodulin in target selection inside cells. |
format | Online Article Text |
id | pubmed-3145654 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31456542011-08-09 The Effect of Macromolecular Crowding, Ionic Strength and Calcium Binding on Calmodulin Dynamics Wang, Qian Liang, Kao-Chen Czader, Arkadiusz Waxham, M. Neal Cheung, Margaret S. PLoS Comput Biol Research Article The flexibility in the structure of calmodulin (CaM) allows its binding to over 300 target proteins in the cell. To investigate the structure-function relationship of CaM, we combined methods of computer simulation and experiments based on circular dichroism (CD) to investigate the structural characteristics of CaM that influence its target recognition in crowded cell-like conditions. We developed a unique multiscale solution of charges computed from quantum chemistry, together with protein reconstruction, coarse-grained molecular simulations, and statistical physics, to represent the charge distribution in the transition from apoCaM to holoCaM upon calcium binding. Computationally, we found that increased levels of macromolecular crowding, in addition to calcium binding and ionic strength typical of that found inside cells, can impact the conformation, helicity and the EF hand orientation of CaM. Because EF hand orientation impacts the affinity of calcium binding and the specificity of CaM's target selection, our results may provide unique insight into understanding the promiscuous behavior of calmodulin in target selection inside cells. Public Library of Science 2011-07-28 /pmc/articles/PMC3145654/ /pubmed/21829336 http://dx.doi.org/10.1371/journal.pcbi.1002114 Text en Wang 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 Wang, Qian Liang, Kao-Chen Czader, Arkadiusz Waxham, M. Neal Cheung, Margaret S. The Effect of Macromolecular Crowding, Ionic Strength and Calcium Binding on Calmodulin Dynamics |
title | The Effect of Macromolecular Crowding, Ionic Strength and Calcium Binding on Calmodulin Dynamics |
title_full | The Effect of Macromolecular Crowding, Ionic Strength and Calcium Binding on Calmodulin Dynamics |
title_fullStr | The Effect of Macromolecular Crowding, Ionic Strength and Calcium Binding on Calmodulin Dynamics |
title_full_unstemmed | The Effect of Macromolecular Crowding, Ionic Strength and Calcium Binding on Calmodulin Dynamics |
title_short | The Effect of Macromolecular Crowding, Ionic Strength and Calcium Binding on Calmodulin Dynamics |
title_sort | effect of macromolecular crowding, ionic strength and calcium binding on calmodulin dynamics |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145654/ https://www.ncbi.nlm.nih.gov/pubmed/21829336 http://dx.doi.org/10.1371/journal.pcbi.1002114 |
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