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The thermodynamic stability of proteins and regulation of their functional activity can be described within the energy landscape framework, where the former is provided by a unique native conformational ensemble separated by an energy gap from misfolded structures, and the latter is based on conformational transitions between structural states in the native ensemble. This work investigates the relationship between fundamentals of structural stability and dynamics-driven allosteric regulation. We describe here general proteomic trends and fold/function-specific determinants of protein stability. The intricate relationship between stability and allostery has been observed, showing how requirements on stability and thermal adaptation drive and shape the protein's "structural platform", while complementary sequence-structure determinants control the allosteric signaling and regulation. We illustrate our findings using four groups of proteins - inorganic pyrophosphatase and β-glucosidase representing hydrolases, the CheY signaling protein, and adenylate kinase - obtained from host organisms spanning from psychrophiles to hyperthermophiles. We also show that allosteric effects of mutations in adenylate kinase account for experimentally observed changes in organismal fitness expressed in bacterial growth rates. Epistasis arising from the effects of these mutations is another important phenomenon, resulting in unexpected non-additive changes in fitness that could not be explained by the stability changes alone. The findings in this work and options for further investigations of the stability-signaling relationship are provided by the sequence-dependent model of allostery employed here and implemented in AlloSigMA 3 - the latest update of our AlloSigMA web-server (https://allosigma.bii.a-star.edu.sg).
Raechell et al. (Tue,) studied this question.