The conformational ensemble and function of intrinsically disordered proteins (IDPs) are sensitive to their solution environment. The inherent malleability of disordered proteins combined with the exposure of their residues accounts for this sensitivity. One context in which IDPs play important roles that is concomitant with massive changes to intracellular chemistry is during extreme environmental stress (e.g., desiccation or freezing). The ability of organisms to survive these stresses has long been linked to the accumulation of high levels of cosolutes, such as trehalose, sucrose, or glycerol, as well as the enrichment of IDPs, such as late embryogenesis abundant (LEA) proteins or cytoplasmic abundant heat soluble (CAHS) proteins. Despite knowing that IDPs play important roles and are co-enriched alongside endogenous, species-specific cosolutes during environmental stress, little is known mechanistically about how IDP-cosolute interactions influence tolerance to these stresses. Here, we test the notion that the protective function of stress-related IDPs is enhanced through conformational changes induced by endogenous cosolutes. We find that desiccation-related IDPs derived from four different organisms spanning two LEA protein families and the CAHS protein family, synergize best with endogenous cosolutes during drying to promote desiccation protection. We show that when mixed with small molecules enriched under different stress conditions the same IDP is functionally tuned to protect biological material from the corresponding stress under which the cosolute is enriched. Our results suggest that functional synergy between IDPs and endogenous cosolutes is a convergent protection strategy seen among different IDP families and organisms, yet the mechanisms underlying this synergy differ between IDP families.
Thomas E. Boothby (Sun,) studied this question.