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Decrease in pH destabilizes individual vault nanocages by weakening the inter-protein lateral interaction

Vault particles are naturally occurring proteinaceous cages with promising application as molecular containers. The use of vaults as functional transporters requires a profound understanding of their structural stability to guarantee the protection and controlled payload delivery. Previous results p...

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Autores principales: Llauró, Aida, Guerra, Pablo, Kant, Ravi, Bothner, Brian, Verdaguer, Núria, de Pablo, Pedro J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064368/
https://www.ncbi.nlm.nih.gov/pubmed/27739422
http://dx.doi.org/10.1038/srep34143
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author Llauró, Aida
Guerra, Pablo
Kant, Ravi
Bothner, Brian
Verdaguer, Núria
de Pablo, Pedro J.
author_facet Llauró, Aida
Guerra, Pablo
Kant, Ravi
Bothner, Brian
Verdaguer, Núria
de Pablo, Pedro J.
author_sort Llauró, Aida
collection PubMed
description Vault particles are naturally occurring proteinaceous cages with promising application as molecular containers. The use of vaults as functional transporters requires a profound understanding of their structural stability to guarantee the protection and controlled payload delivery. Previous results performed with bulk techniques or at non-physiological conditions have suggested pH as a parameter to control vault dynamics. Here we use Atomic Force Microscopy (AFM) to monitor the structural evolution of individual vault particles while changing the pH in real time. Our experiments show that decreasing the pH of the solution destabilize the barrel region, the central part of vault particles, and leads to the aggregation of the cages. Additional analyses using Quartz-Crystal Microbalance (QCM) and Differential Scanning Fluorimetry (DSF) are consistent with our single molecule AFM experiments. The observed topographical defects suggest that low pH weakens the bonds between adjacent proteins. We hypothesize that the observed effects are related to the strong polar character of the protein-protein lateral interactions. Overall, our study unveils the mechanism for the influence of a biologically relevant range of pHs on the stability and dynamics of vault particles.
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spelling pubmed-50643682016-10-26 Decrease in pH destabilizes individual vault nanocages by weakening the inter-protein lateral interaction Llauró, Aida Guerra, Pablo Kant, Ravi Bothner, Brian Verdaguer, Núria de Pablo, Pedro J. Sci Rep Article Vault particles are naturally occurring proteinaceous cages with promising application as molecular containers. The use of vaults as functional transporters requires a profound understanding of their structural stability to guarantee the protection and controlled payload delivery. Previous results performed with bulk techniques or at non-physiological conditions have suggested pH as a parameter to control vault dynamics. Here we use Atomic Force Microscopy (AFM) to monitor the structural evolution of individual vault particles while changing the pH in real time. Our experiments show that decreasing the pH of the solution destabilize the barrel region, the central part of vault particles, and leads to the aggregation of the cages. Additional analyses using Quartz-Crystal Microbalance (QCM) and Differential Scanning Fluorimetry (DSF) are consistent with our single molecule AFM experiments. The observed topographical defects suggest that low pH weakens the bonds between adjacent proteins. We hypothesize that the observed effects are related to the strong polar character of the protein-protein lateral interactions. Overall, our study unveils the mechanism for the influence of a biologically relevant range of pHs on the stability and dynamics of vault particles. Nature Publishing Group 2016-10-14 /pmc/articles/PMC5064368/ /pubmed/27739422 http://dx.doi.org/10.1038/srep34143 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Llauró, Aida
Guerra, Pablo
Kant, Ravi
Bothner, Brian
Verdaguer, Núria
de Pablo, Pedro J.
Decrease in pH destabilizes individual vault nanocages by weakening the inter-protein lateral interaction
title Decrease in pH destabilizes individual vault nanocages by weakening the inter-protein lateral interaction
title_full Decrease in pH destabilizes individual vault nanocages by weakening the inter-protein lateral interaction
title_fullStr Decrease in pH destabilizes individual vault nanocages by weakening the inter-protein lateral interaction
title_full_unstemmed Decrease in pH destabilizes individual vault nanocages by weakening the inter-protein lateral interaction
title_short Decrease in pH destabilizes individual vault nanocages by weakening the inter-protein lateral interaction
title_sort decrease in ph destabilizes individual vault nanocages by weakening the inter-protein lateral interaction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064368/
https://www.ncbi.nlm.nih.gov/pubmed/27739422
http://dx.doi.org/10.1038/srep34143
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