Protein surface chemistry encodes an adaptive tolerance to desiccation

Cellular desiccation - the loss of nearly all water from the cell - is a recurring stress in an increasing number of ecosystems that can drive proteome-wide protein unfolding and aggregation. For cells to survive this stress, at least some of the proteome must disaggregate and resume function upon rehydration. The molecular determinants that underlie the ability of proteins to do this remain largely unknown. Here, we apply quantitative and structural proteomic mass spectrometry to desiccated and rehydrated yeast extracts to show that some proteins possess an innate capacity to survive extreme water loss. Structural analysis correlates the ability of proteins to tolerate desiccation with their surface chemistry. We find that highly tolerant proteins are responsible for the production of the cell’s building blocks - amino acids, metabolites, and sugars. Conversely, those proteins that are most desiccation-sensitive are involved in ribosome biogenesis and other energy consuming processes. As a result, the rehydrated proteome is preferentially enriched with metabolite and small molecule producers and depleted of some of the cell’s heaviest consumers. We propose this functional bias enables cells to kickstart their metabolism and promote cell survival following desiccation and rehydration.