Low temperature under high pressure physically traps the troponin C N-domain in a conformation mimicking the calcium-bound state, demonstrating that hydrophobic core exposure is an enthalpy-driven process.
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No immediate clinical implications for troponin-targeted therapies; leaves open thermodynamic drivers of cardiac muscle regulation in vivo.
Calcium binding to the N-domain of troponin C initiates a series of conformational changes that lead to muscle contraction. Calcium binding provides the free energy for a hydrophobic region in the core of N-domain to assume a more open configuration. Fluorescence measurements on a tryptophan mutant (F29W) show that a similar conformational change occurs in the absence of Ca2+ when the temperature is lowered under pressure. The conformation induced by subzero temperatures binds the hydrophobic probe bis-aminonaphthalene sulfonate, and the tryptophan has the same fluorescence lifetime (7 ns) as in the Ca2+-bound form. The decrease in volume (delta V = -25.4 ml/mol) corresponds to an increase in surface area. Thermodynamic measurements suggest an enthalpy-driven conformational change that leads to an intermediate with an exposed N-domain core and a high affinity for Ca2+.
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Foguel et al. (1996) studied this question.
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