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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
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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. |
format | Online Article Text |
id | pubmed-6506438 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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