Abstract
Protein folding thermodynamics can determine the contribution of protein fluctuation, which is difficult to detect but critical for protein function. We have analyzed the structural dynamic properties of the DNA-binding domain of a transcriptional activator, c-Myb R2R3. Earlier reports state that a substitution at the linker between R2 and R3 resulted in a significant loss of affinity toward the cognate DNA, mainly due to increased entropy in the DNA-unbound state. In this study, we analyzed the effects of the linker on folding stability and found that mutation of Pro140 to Gly or Ala resulted in decreased stability, due to an unfavorable enthalpy change that was only partially compensated by a favorable entropy change. Considering that the mutation would increase protein fluctuations in both the folded and unfolded states, we assume that the change in the folded state would be larger than in the unfolded state. This is perhaps due to the additional intramolecular interactions that only occur in the folded state. The increase in protein fluctuation in the folded state post-mutation was correlated with protein function, as reported previously.
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The present article is based on the lecture presented at JCCTA50 conference in Osaka – Japan on 28–30 September, 2014.
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Inaba, S., Fukada, H. & Oda, M. Thermodynamic effects of a linker region between two repeats of a protein, c-Myb R2R3, on its stability and structural dynamics. J Therm Anal Calorim 123, 1763–1767 (2016). https://doi.org/10.1007/s10973-015-4812-9
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DOI: https://doi.org/10.1007/s10973-015-4812-9