Proteome-wide observation of the phenomenon of life on the edge of solubility.
Dobson, Christopher M
Hartl, F Ulrich
Proceedings of the National Academy of Sciences of the United States of America, volume 117, issue 2
MetadataShow full item record
Vecchi, G., Sormanni, P., Mannini, B., Vandelli, A., Tartaglia, G. G., Dobson, C. M., Hartl, F. U., & et al. (2019). Proteome-wide observation of the phenomenon of life on the edge of solubility.. Proceedings of the National Academy of Sciences of the United States of America, volume 117, issue 2 https://doi.org/10.1073/pnas.1910444117
To function effectively proteins must avoid aberrant aggregation, and hence they are expected to be expressed at concentrations safely below their solubility limits. By analyzing proteome-wide mass spectrometry data of Caenorhabditis elegans, however, we show that the levels of about three-quarters of the nearly 4,000 proteins analyzed in adult animals are close to their intrinsic solubility limits, indeed exceeding them by about 10% on average. We next asked how aging and functional self-assembly influence these solubility limits. We found that despite the fact that the total quantity of proteins within the cellular environment remains approximately constant during aging, protein aggregation sharply increases between days 6 and 12 of adulthood, after the worms have reproduced, as individual proteins lose their stoichiometric balances and the cellular machinery that maintains solubility undergoes functional decline. These findings reveal that these proteins are highly prone to undergoing concentration-dependent phase separation, which on aging is rationalized in a decrease of their effective solubilities, in particular for proteins associated with translation, growth, reproduction, and the chaperone system.
Protein aggregation, Protein Homeostasis, Protein Misfolding Diseases
External DOI: https://doi.org/10.1073/pnas.1910444117
This record's URL: https://www.repository.cam.ac.uk/handle/1810/301623
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/