2003 journal article
Equilibrium and kinetic folding of a alpha-helical Greek key protein domain: Caspase recruitment domain (CARD) of RICK
BIOCHEMISTRY, 42(20), 6310–6320.
We have characterized the equilibrium and kinetic folding of a unique protein domain, caspase recruitment domain (CARD), of the RIP-like interacting CLARP kinase (RICK) (RICK-CARD), which adopts a α-helical Greek key fold. At equilibrium, the folding of RICK-CARD is well described by a two-state mechanism representing the native and unfolded ensembles. The protein is marginally stable, with a ΔGH2O of 3.0 ± 0.15 kcal/mol and an m-value of 1.27 ± 0.06 kcal mol-1 M-1 (30 mM Tris-HCl, pH 8, 1 mM DTT, 25 °C). While the m-value is constant, the protein stability decreases in the presence of moderate salt concentrations (below 200 mM) and then increases at higher salt concentrations. The results suggest that electrostatic interactions are stabilizing in the native protein, and the favorable Coulombic interactions are reduced at low ionic strength. Above 200 mM salt, the results are consistent with Hofmeister effects. The unfolding pathway of RICK-CARD is complex and contains at least three non-native conformati...