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Shared dynamics of LeuT superfamily members and allosteric differentiation by structural irregularities and multimerization
The LeuT-fold superfamily includes secondary active transporters from different functional families, which share a common tertiary structure, despite having a remarkably low sequence similarity. By identifying the common structural and dynamical features upon principal component analysis of a compre...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941172/ https://www.ncbi.nlm.nih.gov/pubmed/29735731 http://dx.doi.org/10.1098/rstb.2017.0177 |
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author | Ponzoni, Luca Zhang, She Cheng, Mary Hongying Bahar, Ivet |
author_facet | Ponzoni, Luca Zhang, She Cheng, Mary Hongying Bahar, Ivet |
author_sort | Ponzoni, Luca |
collection | PubMed |
description | The LeuT-fold superfamily includes secondary active transporters from different functional families, which share a common tertiary structure, despite having a remarkably low sequence similarity. By identifying the common structural and dynamical features upon principal component analysis of a comprehensive ensemble of 90 experimentally resolved structures and anisotropic network model evaluation of collective motions, we provide a unified point of view for understanding the reasons why this particular fold has been selected by evolution to accomplish such a broad spectrum of functions. The parallel identification of conserved sequence features, localized at specific sites of transmembrane helices, sheds light on the role of broken helices (TM1 and TM6 in LeuT) in promoting ion/substrate binding and allosteric interconversion between the outward- and inward-facing conformations of transporters. Finally, the determination of the dynamics landscape for the structural ensemble provides a promising framework for the classification of transporters based on their dynamics, and the characterization of the collective movements that favour multimerization. This article is part of a discussion meeting issue ‘Allostery and molecular machines’. |
format | Online Article Text |
id | pubmed-5941172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-59411722018-05-14 Shared dynamics of LeuT superfamily members and allosteric differentiation by structural irregularities and multimerization Ponzoni, Luca Zhang, She Cheng, Mary Hongying Bahar, Ivet Philos Trans R Soc Lond B Biol Sci Articles The LeuT-fold superfamily includes secondary active transporters from different functional families, which share a common tertiary structure, despite having a remarkably low sequence similarity. By identifying the common structural and dynamical features upon principal component analysis of a comprehensive ensemble of 90 experimentally resolved structures and anisotropic network model evaluation of collective motions, we provide a unified point of view for understanding the reasons why this particular fold has been selected by evolution to accomplish such a broad spectrum of functions. The parallel identification of conserved sequence features, localized at specific sites of transmembrane helices, sheds light on the role of broken helices (TM1 and TM6 in LeuT) in promoting ion/substrate binding and allosteric interconversion between the outward- and inward-facing conformations of transporters. Finally, the determination of the dynamics landscape for the structural ensemble provides a promising framework for the classification of transporters based on their dynamics, and the characterization of the collective movements that favour multimerization. This article is part of a discussion meeting issue ‘Allostery and molecular machines’. The Royal Society 2018-06-19 2018-05-07 /pmc/articles/PMC5941172/ /pubmed/29735731 http://dx.doi.org/10.1098/rstb.2017.0177 Text en © 2018 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Articles Ponzoni, Luca Zhang, She Cheng, Mary Hongying Bahar, Ivet Shared dynamics of LeuT superfamily members and allosteric differentiation by structural irregularities and multimerization |
title | Shared dynamics of LeuT superfamily members and allosteric differentiation by structural irregularities and multimerization |
title_full | Shared dynamics of LeuT superfamily members and allosteric differentiation by structural irregularities and multimerization |
title_fullStr | Shared dynamics of LeuT superfamily members and allosteric differentiation by structural irregularities and multimerization |
title_full_unstemmed | Shared dynamics of LeuT superfamily members and allosteric differentiation by structural irregularities and multimerization |
title_short | Shared dynamics of LeuT superfamily members and allosteric differentiation by structural irregularities and multimerization |
title_sort | shared dynamics of leut superfamily members and allosteric differentiation by structural irregularities and multimerization |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941172/ https://www.ncbi.nlm.nih.gov/pubmed/29735731 http://dx.doi.org/10.1098/rstb.2017.0177 |
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