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Soluble expression of proteins correlates with a lack of positively-charged surface

Prediction of protein solubility is gaining importance with the growing use of protein molecules as therapeutics, and ongoing requirements for high level expression. We have investigated protein surface features that correlate with insolubility. Non-polar surface patches associate to some degree wit...

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Detalles Bibliográficos
Autores principales: Chan, Pedro, Curtis, Robin A., Warwicker, Jim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506438/
https://www.ncbi.nlm.nih.gov/pubmed/24276756
http://dx.doi.org/10.1038/srep03333
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author Chan, Pedro
Curtis, Robin A.
Warwicker, Jim
author_facet Chan, Pedro
Curtis, Robin A.
Warwicker, Jim
author_sort Chan, Pedro
collection PubMed
description Prediction of protein solubility is gaining importance with the growing use of protein molecules as therapeutics, and ongoing requirements for high level expression. We have investigated protein surface features that correlate with insolubility. Non-polar surface patches associate to some degree with insolubility, but this is far exceeded by the association with positively-charged patches. Negatively-charged patches do not separate insoluble/soluble subsets. The separation of soluble and insoluble subsets by positive charge clustering (area under the curve for a ROC plot is 0.85) has a striking parallel with the separation that delineates nucleic acid-binding proteins, although most of the insoluble dataset are not known to bind nucleic acid. Additionally, these basic patches are enriched for arginine, relative to lysine. The results are discussed in the context of expression systems and downstream processing, contributing to a view of protein solubility in which the molecular interactions of charged groups are far from equivalent.
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spelling pubmed-65064382019-05-21 Soluble expression of proteins correlates with a lack of positively-charged surface Chan, Pedro Curtis, Robin A. Warwicker, Jim Sci Rep Article Prediction of protein solubility is gaining importance with the growing use of protein molecules as therapeutics, and ongoing requirements for high level expression. We have investigated protein surface features that correlate with insolubility. Non-polar surface patches associate to some degree with insolubility, but this is far exceeded by the association with positively-charged patches. Negatively-charged patches do not separate insoluble/soluble subsets. The separation of soluble and insoluble subsets by positive charge clustering (area under the curve for a ROC plot is 0.85) has a striking parallel with the separation that delineates nucleic acid-binding proteins, although most of the insoluble dataset are not known to bind nucleic acid. Additionally, these basic patches are enriched for arginine, relative to lysine. The results are discussed in the context of expression systems and downstream processing, contributing to a view of protein solubility in which the molecular interactions of charged groups are far from equivalent. Nature Publishing Group 2013-11-26 /pmc/articles/PMC6506438/ /pubmed/24276756 http://dx.doi.org/10.1038/srep03333 Text en Copyright © 2013, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
spellingShingle Article
Chan, Pedro
Curtis, Robin A.
Warwicker, Jim
Soluble expression of proteins correlates with a lack of positively-charged surface
title Soluble expression of proteins correlates with a lack of positively-charged surface
title_full Soluble expression of proteins correlates with a lack of positively-charged surface
title_fullStr Soluble expression of proteins correlates with a lack of positively-charged surface
title_full_unstemmed Soluble expression of proteins correlates with a lack of positively-charged surface
title_short Soluble expression of proteins correlates with a lack of positively-charged surface
title_sort soluble expression of proteins correlates with a lack of positively-charged surface
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506438/
https://www.ncbi.nlm.nih.gov/pubmed/24276756
http://dx.doi.org/10.1038/srep03333
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