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Proteins must be hydrated to function. Desiccation, a common event in an increasing number of ecosystems, can drive proteome-wide unfolding and aggregation. For cells to survive, proteins must disaggregate and retain their function upon rehydration. The molecular determinants that underlie protein desiccation resistance remain unknown. Here, we use mass spectrometry to show that some proteins possess an innate ability to survive dehydration and subsequent rehydration. Structural analysis correlates the ability of proteins to resist desiccation with their surface area chemistry. Remarkably, highly resistant proteins are responsible for the production of the cell's building blocks - amino acids, metabolites, and sugars. Conversely, those proteins that are desiccation-sensitive are responsible for ribosome biogenesis. As a result, the rehydrated proteome is preferentially enriched with metabolite and small molecule producers and depleted of ribosomes - the cell's heaviest consumers. We propose this functional bias allows cells to kickstart their metabolism and promote cell survival upon rehydration.
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Protein surface chemistry encodes an adaptive tolerance to desiccation
Cellular desiccation—the loss of nearly all water from the cell—is a recurring stress that drives widespread protein dysfunction. To survive, part of the proteome must resume function upon rehydration. Which proteins tolerate desiccation, and the molecular determinants that underlie this tolerance, are largely unknown. Here, we use quantitative mass spectrometry and structural proteomics to show that certain proteins possess an innate capacity to tolerate extreme water loss. Structural analyses point to protein surface chemistry as a key determinant of desiccation tolerance, which we test by showing that rational surface mutants can convert a desiccation-sensitive protein into a tolerant one. We also find that highly tolerant proteins are responsible for the production of small-molecule building blocks, while intolerant proteins are involved in energy-consuming processes such as ribosome biogenesis. We propose that this functional bias enables cells to kickstart their metabolism and promote cell survival following desiccation and rehydration. A record of this paper’s transparent peer review process is included in the supplemental information.
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- PAR ID:
- 10681347
- Publisher / Repository:
- Cell Systems
- Date Published:
- Journal Name:
- Cell Systems
- Volume:
- 16
- Issue:
- 10
- ISSN:
- 2405-4712
- Page Range / eLocation ID:
- 101407
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript
- Journal Article:
- https://doi.org/10.1016/j.cels.2025.101407
