DOI: 10.1002/anie.201309317. Interaction with the Surrounding Water Plays a Key Role in Determining the Aggregation Propensity of Proteins

Interaction with the Surrounding Water Plays a Key Role in Determining the Aggregation Propensity of Proteins

10.1002/anie.201309317

Crossref journal-article

Wiley

Angewandte Chemie International Edition (311)

Abstract

AbstractUnderstanding the molecular determinants of the relative propensities of proteins to aggregate in a cellular environment is a central issue for treating protein‐aggregation diseases and developing peptide‐based therapeutics. Despite the expectation that protein aggregation can largely be attributed to direct protein–protein interactions, a crucial role the surrounding water in determining the aggregation propensity of proteins both in vitro and in vivo was identified. The overall protein hydrophobicity, defined solely by the hydration free energy of a protein in its monomeric state sampling its equilibrium structures, was shown to be the predominant determinant of protein aggregation propensity in aqueous solution. Striking discrimination of positively and negatively charged residues by the surrounding water was also found. This effect depends on the protein net charge and plays a crucial role in regulating the solubility of the protein. These results pave the way for the design of aggregation‐resistant proteins as biotherapeutics.

Bibliography

Chong, S., & Ham, S. (2014). Interaction with the Surrounding Water Plays a Key Role in Determining the Aggregation Propensity of Proteins. Angewandte Chemie International Edition, 53(15), 3961â3964. Portico.

Authors 2

Song‐Ho Chong (first)
Sihyun Ham (additional)

References 32 Referenced 93

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Dates

Type	When
Created	11 years, 6 months ago (Feb. 24, 2014, 4:27 p.m.)
Deposited	1 year, 10 months ago (Oct. 16, 2023, 11:46 a.m.)
Indexed	2 weeks, 4 days ago (Aug. 19, 2025, 7:06 a.m.)
Issued	11 years, 6 months ago (Feb. 24, 2014)
Published	11 years, 6 months ago (Feb. 24, 2014)
Published Online	11 years, 6 months ago (Feb. 24, 2014)
Published Print	11 years, 4 months ago (April 7, 2014)

Funders 0

None

BibTeX

@article{Chong_2014, title={Interaction with the Surrounding Water Plays a Key Role in Determining the Aggregation Propensity of Proteins}, volume={53}, ISSN={1521-3773}, url={http://dx.doi.org/10.1002/anie.201309317}, DOI={10.1002/anie.201309317}, number={15}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Chong, Song‐Ho and Ham, Sihyun}, year={2014}, month=feb, pages={3961–3964} }

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