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Artículo

Optimization of Conformational Dynamics in an Epistatic Evolutionary Trajectory

Gonzalez, Mariano MartinIcon ; Abriata, Luciano AndresIcon ; Tomatis, Pablo EmilianoIcon ; Vila, Alejandro JoseIcon
Fecha de publicación: 07/2016
Editorial: Oxford University Press
Revista: Molecular Biology and Evolution
ISSN: 1537-1719
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Ciencias Biológicas

Resumen

The understanding of protein evolution depends on the ability to relate the impact of mutations on molecular traits to organismal fitness. Biological activity and robustness have been regarded as important features in shaping protein evolutionary landscapes. Conformational dynamics, which is essential for protein function, has received little attention in the context of evolutionary analyses. Here we employ NMR spectroscopy, the chief experimental tool to describe protein dynamics at atomic level in solution at room temperature, to study the intrinsic dynamic features of a metallo- Β: -lactamase enzyme and three variants identified during a directed evolution experiment that led to an expanded substrate profile. We show that conformational dynamics in the catalytically relevant microsecond to millisecond timescale is optimized along the favored evolutionary trajectory. In addition, we observe that the effects of mutations on dynamics are epistatic. Mutation Gly262Ser introduces slow dynamics on several residues that surround the active site when introduced in the wild-type enzyme. Mutation Asn70Ser removes the slow dynamics observed for few residues of the wild-type enzyme, but increases the number of residues that undergo slow dynamics when introduced in the Gly262Ser mutant. These effects on dynamics correlate with the epistatic interaction between these two mutations on the bacterial phenotype. These findings indicate that conformational dynamics is an evolvable trait, and that proteins endowed with more dynamic active sites also display a larger potential for promoting evolution.
Palabras clave: Conformational Dynamics. , Epistasis , Protein Evolution
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/50472
DOI: http://dx.doi.org/10.1093/molbev/msw052
URL: https://academic.oup.com/mbe/article/33/7/1768/2578968
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Articulos(IBR)
Articulos de INST.DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Citación
Gonzalez, Mariano Martin; Abriata, Luciano Andres; Tomatis, Pablo Emiliano; Vila, Alejandro Jose; Optimization of Conformational Dynamics in an Epistatic Evolutionary Trajectory; Oxford University Press; Molecular Biology and Evolution; 33; 7; 7-2016; 1768-1776
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