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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...

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Detalles Bibliográficos
Autores principales: Ponzoni, Luca, Zhang, She, Cheng, Mary Hongying, Bahar, Ivet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2018
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
Descripción
Sumario: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’.