Romero-Pérez Paulette Sofía, Moran Haley M, Horani Azeem, Truong Alexander, Manriquez-Sandoval Edgar, Ramirez John F, Martinez Alec, Gollub Edith, Hunter Kara, Lotthammer Jeffrey M, Emenecker Ryan J, Liu Hui, Iwasa Janet H, Boothby Thomas C, Holehouse Alex S, Fried Stephen D, Sukenik Shahar
Dept of Chemistry and Biochemistry, University of California Merced, Merced, CA 95343, USA.
Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, USA.
bioRxiv. 2024 Oct 10:2024.07.28.604841. doi: 10.1101/2024.07.28.604841.
Cellular desiccation - the loss of nearly all water from the cell - is a recurring stress in an increasing number of ecosystems that can drive protein unfolding and aggregation. For cells to survive, at least some 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 apply quantitative and structural proteomic mass spectrometry to show that certain proteins possess an innate capacity to tolerate rehydration following extreme water loss. Structural analysis points to protein surface chemistry as a key determinant for desiccation tolerance, which we test by showing that rational surface mutants can convert a desiccation sensitive protein into a tolerant one. Desiccation tolerance also has strong overlap with cellular function, with highly tolerant proteins responsible for production of small molecule building blocks, and intolerant proteins involved in energy-consuming processes such as ribosome biogenesis. 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.
细胞脱水——细胞内几乎所有水分的流失——在越来越多的生态系统中是一种反复出现的应激因素，它会导致蛋白质展开和聚集。为了使细胞存活，至少部分蛋白质组在重新水化后必须恢复功能。哪些蛋白质能够耐受脱水，以及这种耐受性背后的分子决定因素，在很大程度上尚不清楚。在这里，我们应用定量和结构蛋白质组质谱技术表明，某些蛋白质具有在极端水分流失后耐受重新水化的先天能力。结构分析表明蛋白质表面化学是脱水耐受性的关键决定因素，我们通过证明合理的表面突变体可以将对脱水敏感的蛋白质转化为耐受性蛋白质来进行验证。脱水耐受性也与细胞功能有很强的重叠，高度耐受的蛋白质负责小分子构件的产生，而不耐受的蛋白质参与核糖体生物发生等耗能过程。因此，重新水化后的蛋白质组优先富集代谢物和小分子生产者，并耗尽细胞中一些消耗最大的成分。我们认为这种功能偏向使细胞能够在脱水和重新水化后启动其新陈代谢并促进细胞存活。
