Cargando…

Linking protein structural and functional change to mutation using amino acid networks

The function of a protein is strongly dependent on its structure. During evolution, proteins acquire new functions through mutations in the amino-acid sequence. Given the advance in deep mutational scanning, recent findings have found functional change to be position dependent, notwithstanding the c...

Descripción completa

Detalles Bibliográficos
Autores principales: Sotomayor-Vivas, Cristina, Hernández-Lemus, Enrique, Dorantes-Gilardi, Rodrigo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782487/
https://www.ncbi.nlm.nih.gov/pubmed/35061689
http://dx.doi.org/10.1371/journal.pone.0261829
_version_ 1784638326497607680
author Sotomayor-Vivas, Cristina
Hernández-Lemus, Enrique
Dorantes-Gilardi, Rodrigo
author_facet Sotomayor-Vivas, Cristina
Hernández-Lemus, Enrique
Dorantes-Gilardi, Rodrigo
author_sort Sotomayor-Vivas, Cristina
collection PubMed
description The function of a protein is strongly dependent on its structure. During evolution, proteins acquire new functions through mutations in the amino-acid sequence. Given the advance in deep mutational scanning, recent findings have found functional change to be position dependent, notwithstanding the chemical properties of mutant and mutated amino acids. This could indicate that structural properties of a given position are potentially responsible for the functional relevance of a mutation. Here, we looked at the relation between structure and function of positions using five proteins with experimental data of functional change available. In order to measure structural change, we modeled mutated proteins via amino-acid networks and quantified the perturbation of each mutation. We found that structural change is position dependent, and strongly related to functional change. Strong changes in protein structure correlate with functional loss, and positions with functional gain due to mutations tend to be structurally robust. Finally, we constructed a computational method to predict functionally sensitive positions to mutations using structural change that performs well on all five proteins with a mean precision of 74.7% and recall of 69.3% of all functional positions.
format Online
Article
Text
id pubmed-8782487
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-87824872022-01-22 Linking protein structural and functional change to mutation using amino acid networks Sotomayor-Vivas, Cristina Hernández-Lemus, Enrique Dorantes-Gilardi, Rodrigo PLoS One Research Article The function of a protein is strongly dependent on its structure. During evolution, proteins acquire new functions through mutations in the amino-acid sequence. Given the advance in deep mutational scanning, recent findings have found functional change to be position dependent, notwithstanding the chemical properties of mutant and mutated amino acids. This could indicate that structural properties of a given position are potentially responsible for the functional relevance of a mutation. Here, we looked at the relation between structure and function of positions using five proteins with experimental data of functional change available. In order to measure structural change, we modeled mutated proteins via amino-acid networks and quantified the perturbation of each mutation. We found that structural change is position dependent, and strongly related to functional change. Strong changes in protein structure correlate with functional loss, and positions with functional gain due to mutations tend to be structurally robust. Finally, we constructed a computational method to predict functionally sensitive positions to mutations using structural change that performs well on all five proteins with a mean precision of 74.7% and recall of 69.3% of all functional positions. Public Library of Science 2022-01-21 /pmc/articles/PMC8782487/ /pubmed/35061689 http://dx.doi.org/10.1371/journal.pone.0261829 Text en © 2022 Sotomayor-Vivas et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sotomayor-Vivas, Cristina
Hernández-Lemus, Enrique
Dorantes-Gilardi, Rodrigo
Linking protein structural and functional change to mutation using amino acid networks
title Linking protein structural and functional change to mutation using amino acid networks
title_full Linking protein structural and functional change to mutation using amino acid networks
title_fullStr Linking protein structural and functional change to mutation using amino acid networks
title_full_unstemmed Linking protein structural and functional change to mutation using amino acid networks
title_short Linking protein structural and functional change to mutation using amino acid networks
title_sort linking protein structural and functional change to mutation using amino acid networks
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782487/
https://www.ncbi.nlm.nih.gov/pubmed/35061689
http://dx.doi.org/10.1371/journal.pone.0261829
work_keys_str_mv AT sotomayorvivascristina linkingproteinstructuralandfunctionalchangetomutationusingaminoacidnetworks
AT hernandezlemusenrique linkingproteinstructuralandfunctionalchangetomutationusingaminoacidnetworks
AT dorantesgilardirodrigo linkingproteinstructuralandfunctionalchangetomutationusingaminoacidnetworks