Intrinsically Disordered Proteins Synergize with Endogenous Cosolutes to Enhance Desiccation Tolerance
Core Concepts
Desiccation-related intrinsically disordered proteins (IDPs) from different organisms synergize best with their endogenous cosolutes to promote desiccation protection, and this synergy is mediated through distinct mechanisms between IDP families.
Abstract
The study examines the interplay between IDP sequence, solution environment, ensemble, and function in the context of desiccation tolerance. Key highlights:
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Full-length desiccation-related IDPs, including LEA_4, LEA_1, and CAHS proteins, show synergistic protection of a desiccation-sensitive enzyme (LDH) when combined with their endogenous cosolutes (e.g., trehalose, sucrose) compared to exogenous cosolutes.
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This synergistic protection is not observed with short LEA motifs, suggesting the importance of the full-length IDP sequence beyond just the conserved motifs.
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The synergistic protection is not accompanied by detectable changes in the secondary or tertiary structure of the IDPs, indicating that local ensemble changes are not the driving mechanism.
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For the CAHS protein, the synergy is linked to cosolute-induced oligomerization and gelation, which is not observed for the LEA proteins.
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The degree of synergy for CAHS correlates with the transfer free energy of the cosolute, suggesting direct cosolute-IDP interactions drive the synergistic protection. This mechanism does not apply to the LEA proteins.
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The results demonstrate that while functional synergy between IDPs and cosolutes is a convergent desiccation protection strategy, the underlying mechanisms can differ between IDP families.
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Disordered proteins interact with the chemical environment to tune their protective function during drying
Stats
Protective dose 50 (PD50) values for LEA motifs and cosolutes in LDH protection assay.
Percent synergy values for LEA motifs and full-length IDPs with trehalose and sucrose.
Radius of gyration and molecular weight values from SAXS analysis for IDPs and cosolutes.
Enthalpy of melting values from DSC analysis for CAHS D and cosolutes.
Quotes
"Desiccation-related IDPs are enriched in organisms alongside specific cosolutes during drying"
"LEA motifs are not sufficient to mediate synergistic interaction with endogenous cosolutes during desiccation"
"Full-length desiccation-related IDPs act synergistically with cosolutes"
"Trehalose and sucrose do not elicit local ensemble changes to desiccation-related IDPs in solution or in the dry state"
"Trehalose and sucrose promote oligomerization and gelation of CAHS D but not LEA proteins"
"Direct cosolute:IDP interactions drive synergy for CAHS D, but not LEA proteins"
Deeper Inquiries
How do the mechanisms underlying synergy between IDPs and cosolutes differ across other IDP families beyond LEA and CAHS proteins
The mechanisms underlying synergy between IDPs and cosolutes can differ across other IDP families beyond LEA and CAHS proteins due to the unique structural and functional characteristics of each protein family. For example, other IDP families may have distinct sequence motifs or domains that interact differently with cosolutes, leading to varied effects on protein function. Additionally, the oligomerization behavior, conformational flexibility, and specific interactions with cosolutes can vary among different IDP families, influencing the overall synergy observed. These differences in molecular interactions and structural features contribute to the diverse mechanisms of synergy seen across various IDP families.
What are the evolutionary pressures that have led to the divergent synergistic mechanisms observed between these IDP families
The divergent synergistic mechanisms observed between different IDP families can be attributed to evolutionary pressures that have shaped the adaptation of these proteins to specific environmental conditions. Evolutionary processes have likely driven the selection of IDPs that can interact effectively with endogenous cosolutes to enhance desiccation tolerance. Over time, natural selection may have favored IDP sequences that exhibit optimal synergy with the cosolutes present in the cellular environment during desiccation. As a result, IDP families have evolved distinct structural and functional properties that allow them to interact synergistically with specific cosolutes, reflecting the adaptation of organisms to survive extreme drying conditions.
Could the insights gained from understanding IDP-cosolute synergy be leveraged to develop novel desiccation tolerance strategies in non-anhydrobiotic organisms
The insights gained from understanding IDP-cosolute synergy could be leveraged to develop novel desiccation tolerance strategies in non-anhydrobiotic organisms by harnessing the principles of protein-cosolute interactions. By studying the mechanisms of synergy between IDPs and cosolutes, researchers can identify key molecular interactions and structural features that contribute to enhanced desiccation protection. This knowledge can inform the design of synthetic proteins or peptides that mimic the synergistic behavior of natural IDPs, allowing for the development of novel strategies to improve the desiccation tolerance of non-anhydrobiotic organisms. Additionally, understanding the evolutionary basis of IDP-cosolute interactions can guide the engineering of proteins with enhanced resilience to environmental stressors, providing new avenues for biotechnological applications in agriculture, biomedicine, and other fields.
