Interactions between the protein barnase and co-solutes studied by NMR

Abstract

Protein solubility and stability depend on the co-solutes present. There is little theoretical basis for selection of suitable co-solutes. Some guidance is provided by the Hofmeister series, an empirical ordering of anions according to their effect on solubility and stability; and by osmolytes, which are small organic molecules produced by cells to allow them to function in stressful environments. Here, NMR titrations of the protein barnase with Hofmeister anions and osmolytes are used to measure and locate binding, and thus to separate binding and bulk solvent effects. We describe a rationalisation of Hofmeister (and inverse Hofmeister) effects, which is similar to the traditional chaotrope/kosmotrope idea but based on solvent fluctuation rather than water withdrawal, and characterise how co-solutes affect protein stability and solubility, based on solvent fluctuations. This provides a coherent explanation for solute effects, and points towards a more rational basis for choice of excipients.

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Item Type:	Article
Authors/Creators:	Trevitt, C.R. https://orcid.org/0009-0000-4417-8781 Yashwanth Kumar, D.R. https://orcid.org/0009-0002-3510-4339 Fowler, N.J. https://orcid.org/0000-0002-6005-935X Williamson, M.P. https://orcid.org/0000-0001-5572-1903
Copyright, Publisher and Additional Information:	© 2024 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords:	Biophysical chemistry; Protein folding; Proteins; Solution-state NMR
Dates:	Published: 28 February 2024 Published (online): 28 February 2024 Accepted: 9 February 2024 Submitted: 5 November 2023
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield)
Depositing User:	Symplectic Sheffield
Date Deposited:	08 Mar 2024 17:03
Last Modified:	08 Mar 2024 17:03
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	10.1038/s42004-024-01127-0
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:209869

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Interactions between the protein barnase and co-solutes studied by NMR

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