Nasralla, M. orcid.org/0000-0001-8915-9015, Laurent, H. orcid.org/0000-0002-8925-4773, Alderman, O.L.G. orcid.org/0000-0002-2342-811X et al. (2 more authors) (2024) Trimethylamine-N-oxide depletes urea in a peptide solvation shell. Proceedings of the National Academy of Sciences, 121 (14). e2317825121. ISSN 0027-8424
Abstract
Trimethylamine-N-oxide (TMAO) and urea are metabolites that are used by some marine animals to maintain their cell volume in a saline environment. Urea is a well-known denaturant, and TMAO is a protective osmolyte that counteracts urea-induced protein denaturation. TMAO also has a general protein-protective effect, for example, it counters pressure-induced protein denaturation in deep-sea fish. These opposing effects on protein stability have been linked to the spatial relationship of TMAO, urea, and protein molecules. It is generally accepted that urea-induced denaturation proceeds through the accumulation of urea at the protein surface and their subsequent interaction. In contrast, it has been suggested that TMAO’s protein-stabilizing effects stem from its exclusion from the protein surface, and its ability to deplete urea from protein surfaces; however, these spatial relationships are uncertain. We used neutron diffraction, coupled with structural refinement modeling, to study the spatial associations of TMAO and urea with the tripeptide derivative glycine–proline–glycinamide in aqueous urea, aqueous TMAO, and aqueous urea–TMAO (in the mole ratio 1:2 TMAO:urea). We found that TMAO depleted urea from the peptide’s surface and that while TMAO was not excluded from the tripeptide’s surface, strong atomic interactions between the peptide and TMAO were limited to hydrogen bond donating peptide groups. We found that the repartition of urea, by TMAO, was associated with preferential TMAO–urea bonding and enhanced urea–water hydrogen bonding, thereby anchoring urea in the bulk solution and depleting urea from the peptide surface.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY). |
Keywords: | Animals; Water; Methylamines; Urea; Peptides; Membrane Proteins |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Physics and Astronomy (Leeds) > Molecular & Nanoscale Physics The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Physics and Astronomy (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 09 Apr 2024 15:04 |
Last Modified: | 23 Jan 2025 11:38 |
Status: | Published |
Publisher: | PNAS |
Identification Number: | 10.1073/pnas.2317825121 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:211329 |
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