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Dependency Map of Proteins in the Small Ribosomal Subunit

The assembly of the ribosome has recently become an interesting target for antibiotics in several bacteria. In this work, we extended an analytical procedure to determine native state fluctuations and contact breaking to investigate the protein stability dependence in the 30S small ribosomal subunit...

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Detalles Bibliográficos
Autores principales: Hamacher, Kay, Trylska, Joanna, McCammon, J. Andrew
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364506/
https://www.ncbi.nlm.nih.gov/pubmed/16485038
http://dx.doi.org/10.1371/journal.pcbi.0020010
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author Hamacher, Kay
Trylska, Joanna
McCammon, J. Andrew
author_facet Hamacher, Kay
Trylska, Joanna
McCammon, J. Andrew
author_sort Hamacher, Kay
collection PubMed
description The assembly of the ribosome has recently become an interesting target for antibiotics in several bacteria. In this work, we extended an analytical procedure to determine native state fluctuations and contact breaking to investigate the protein stability dependence in the 30S small ribosomal subunit of Thermus thermophilus. We determined the causal influence of the presence and absence of proteins in the 30S complex on the binding free energies of other proteins. The predicted dependencies are in overall agreement with the experimentally determined assembly map for another organism, Escherichia coli. We found that the causal influences result from two distinct mechanisms: one is pure internal energy change, the other originates from the entropy change. We discuss the implications on how to target the ribosomal assembly most effectively by suggesting six proteins as targets for mutations or other hindering of their binding. Our results show that by blocking one out of this set of proteins, the association of other proteins is eventually reduced, thus reducing the translation efficiency even more. We could additionally determine the binding dependency of THX—a peptide not present in the ribosome of E. coli—and suggest its assembly path.
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spelling pubmed-13645062006-03-27 Dependency Map of Proteins in the Small Ribosomal Subunit Hamacher, Kay Trylska, Joanna McCammon, J. Andrew PLoS Comput Biol Research Article The assembly of the ribosome has recently become an interesting target for antibiotics in several bacteria. In this work, we extended an analytical procedure to determine native state fluctuations and contact breaking to investigate the protein stability dependence in the 30S small ribosomal subunit of Thermus thermophilus. We determined the causal influence of the presence and absence of proteins in the 30S complex on the binding free energies of other proteins. The predicted dependencies are in overall agreement with the experimentally determined assembly map for another organism, Escherichia coli. We found that the causal influences result from two distinct mechanisms: one is pure internal energy change, the other originates from the entropy change. We discuss the implications on how to target the ribosomal assembly most effectively by suggesting six proteins as targets for mutations or other hindering of their binding. Our results show that by blocking one out of this set of proteins, the association of other proteins is eventually reduced, thus reducing the translation efficiency even more. We could additionally determine the binding dependency of THX—a peptide not present in the ribosome of E. coli—and suggest its assembly path. Public Library of Science 2006-02 2006-02-17 /pmc/articles/PMC1364506/ /pubmed/16485038 http://dx.doi.org/10.1371/journal.pcbi.0020010 Text en © 2006 Hamacher 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
Hamacher, Kay
Trylska, Joanna
McCammon, J. Andrew
Dependency Map of Proteins in the Small Ribosomal Subunit
title Dependency Map of Proteins in the Small Ribosomal Subunit
title_full Dependency Map of Proteins in the Small Ribosomal Subunit
title_fullStr Dependency Map of Proteins in the Small Ribosomal Subunit
title_full_unstemmed Dependency Map of Proteins in the Small Ribosomal Subunit
title_short Dependency Map of Proteins in the Small Ribosomal Subunit
title_sort dependency map of proteins in the small ribosomal subunit
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364506/
https://www.ncbi.nlm.nih.gov/pubmed/16485038
http://dx.doi.org/10.1371/journal.pcbi.0020010
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