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Guanidine-HCl Dependent Structural Unfolding of M-Crystallin: Fluctuating Native State Like Topologies and Intermolecular Association
Numerous experimental techniques and computational studies, proposed in recent times, have revolutionized the understanding of protein-folding paradigm. The complete understanding of protein folding and intermediates are of medical relevance, as the aggregation of misfolding proteins underlies vario...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524170/ https://www.ncbi.nlm.nih.gov/pubmed/23284604 http://dx.doi.org/10.1371/journal.pone.0042948 |
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author | Barnwal, Ravi Pratap Agarwal, Geetika Chary, Kandala V. R. |
author_facet | Barnwal, Ravi Pratap Agarwal, Geetika Chary, Kandala V. R. |
author_sort | Barnwal, Ravi Pratap |
collection | PubMed |
description | Numerous experimental techniques and computational studies, proposed in recent times, have revolutionized the understanding of protein-folding paradigm. The complete understanding of protein folding and intermediates are of medical relevance, as the aggregation of misfolding proteins underlies various diseases, including some neurodegenerative disorders. Here, we describe the unfolding of M-crystallin, a βγ-crystallin homologue protein from archaea, from its native state to its denatured state using multidimensional NMR and other biophysical techniques. The protein, which was earlier characterized to be a predominantly β-sheet protein in its native state, shows different structural propensities (α and β), under different denaturing conditions. In 2 M GdmCl, the protein starts showing two distinct sets of peaks, with one arising from a partially unfolded state and the other from a completely folded state. The native secondary structural elements start disappearing as the denaturant concentration approaches 4 M. Subsequently, the protein is completely unfolded when the denaturant concentration is 6 M. The (15)N relaxation data (T(1)/T(2)), heteronuclear (1)H-(15)N Overhauser effects (nOes), NOESY data, and other biophysical data taken together indicate that the protein shows a consistent, gradual change in its structural and motional preferences with increasing GdmCl concentration. |
format | Online Article Text |
id | pubmed-3524170 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35241702013-01-02 Guanidine-HCl Dependent Structural Unfolding of M-Crystallin: Fluctuating Native State Like Topologies and Intermolecular Association Barnwal, Ravi Pratap Agarwal, Geetika Chary, Kandala V. R. PLoS One Research Article Numerous experimental techniques and computational studies, proposed in recent times, have revolutionized the understanding of protein-folding paradigm. The complete understanding of protein folding and intermediates are of medical relevance, as the aggregation of misfolding proteins underlies various diseases, including some neurodegenerative disorders. Here, we describe the unfolding of M-crystallin, a βγ-crystallin homologue protein from archaea, from its native state to its denatured state using multidimensional NMR and other biophysical techniques. The protein, which was earlier characterized to be a predominantly β-sheet protein in its native state, shows different structural propensities (α and β), under different denaturing conditions. In 2 M GdmCl, the protein starts showing two distinct sets of peaks, with one arising from a partially unfolded state and the other from a completely folded state. The native secondary structural elements start disappearing as the denaturant concentration approaches 4 M. Subsequently, the protein is completely unfolded when the denaturant concentration is 6 M. The (15)N relaxation data (T(1)/T(2)), heteronuclear (1)H-(15)N Overhauser effects (nOes), NOESY data, and other biophysical data taken together indicate that the protein shows a consistent, gradual change in its structural and motional preferences with increasing GdmCl concentration. Public Library of Science 2012-12-17 /pmc/articles/PMC3524170/ /pubmed/23284604 http://dx.doi.org/10.1371/journal.pone.0042948 Text en © 2012 Barnwal 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 Barnwal, Ravi Pratap Agarwal, Geetika Chary, Kandala V. R. Guanidine-HCl Dependent Structural Unfolding of M-Crystallin: Fluctuating Native State Like Topologies and Intermolecular Association |
title | Guanidine-HCl Dependent Structural Unfolding of M-Crystallin: Fluctuating Native State Like Topologies and Intermolecular Association |
title_full | Guanidine-HCl Dependent Structural Unfolding of M-Crystallin: Fluctuating Native State Like Topologies and Intermolecular Association |
title_fullStr | Guanidine-HCl Dependent Structural Unfolding of M-Crystallin: Fluctuating Native State Like Topologies and Intermolecular Association |
title_full_unstemmed | Guanidine-HCl Dependent Structural Unfolding of M-Crystallin: Fluctuating Native State Like Topologies and Intermolecular Association |
title_short | Guanidine-HCl Dependent Structural Unfolding of M-Crystallin: Fluctuating Native State Like Topologies and Intermolecular Association |
title_sort | guanidine-hcl dependent structural unfolding of m-crystallin: fluctuating native state like topologies and intermolecular association |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524170/ https://www.ncbi.nlm.nih.gov/pubmed/23284604 http://dx.doi.org/10.1371/journal.pone.0042948 |
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