Protein surface chemistry encodes an adaptive tolerance to desiccation

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Cellular desiccation, the loss of cellular water, leads to protein dysfunction.
• Understanding which proteins tolerate desiccation and the molecular basis of this tolerance is crucial for cell survival.
• The ability of cellular components to resume function after rehydration is key.

Purpose of the Study:

• To identify proteins that intrinsically tolerate cellular desiccation.
• To elucidate the molecular determinants, particularly surface chemistry, of desiccation tolerance.
• To investigate the functional distribution of desiccation-tolerant versus sensitive proteins.

Main Methods:

• Quantitative mass spectrometry to analyze protein abundance and changes.
• Structural proteomics to determine the structural basis of protein tolerance.
• Rational design and mutation of surface residues to test hypotheses on tolerance mechanisms.

Main Results:

• Certain proteins possess an innate capacity to tolerate extreme water loss.
• Protein surface chemistry was identified as a key determinant of desiccation tolerance.
• Rational surface mutants demonstrated the ability to convert sensitive proteins into tolerant ones.
• Highly tolerant proteins are involved in producing building blocks, while sensitive proteins are involved in energy-consuming processes like ribosome biogenesis.

Conclusions:

• Protein surface chemistry is a critical factor in cellular desiccation tolerance.
• A functional bias exists, with tolerant proteins supporting building block synthesis and sensitive proteins involved in energy-intensive processes.
• This bias facilitates metabolic restart and enhances cell survival post-desiccation and rehydration.