Functional synergy between disordered proteins and sugars in desiccation protection.

Abstract

Organisms across all biological kingdoms have evolved to survive near complete desiccation. Desiccation tolerance relies on the intracellular accumulation of high levels of specific intrinsically disordered proteins such as late embryogenesis abundant (LEA) proteins as well as non-reducing disaccharides, such as trehalose and sucrose. IDPs have few intramolecular bonds and a large solvent-accessible surface area, making their ensemble more sensitive to the solution environment than their well-folded counterparts. This implies that the ensemble and functions of protective IDPs are likely to be influenced by changes in metabolome induced by desiccation. Here we show that cosolutes enriched during desiccation, augment the protective function of full length IDPs during drying. We found that trehalose, a key molecule enriched in tardigrades, confers a synergistic protective effect when mixed with a model tardigrade IDP, CAHS D, at biological relevant ratios, and this synergy persists in vivo. Interestingly, a non-tardigrade sugar, sucrose, exerts less synergy. Extending these experiments, we found that LEA proteins from an organism synergizes best with the major non-reducing disaccharide (trehalose or sucrose) enriched in that organism during desiccation to promote protection. LEA proteins are made of 11-mer motif repeats; and interestingly, LEA-sugar synergy is not consistent for 11-, 22-, or 44-mer LEA motifs. Our results demonstrate that desiccation tolerant organisms may have evolved to create a specific cosolute environment to precisely tune the function of constituent IDPs. Beyond extending our knowledge of desiccation tolerance, our finding that cosolutes can tune the protective capacity of IDPs provides evidence that changing solution chemistry can modulate IDP function. We further seek to understand the mechanistic basis of IDP-cosolute synergy using biophysical approaches where we speculate that cosolutes modulate the local and global ensemble of IDPs resulting differences in IDP function.