Protein denaturation convergence temperatures

This value of Tt is the same as the entropic convergence temperature, Tt, observed in proteins (Baldwin, 1986 Murphy etal., 1990). This is the temperature at which the denaturational entropies of globular proteins, normalized to the molecular weight or to the number of amino acid residues, take on nearly the same value when extrapolated under the assumption of constant ACP (Privalov and Khechinashvili, 1974). The significance and interpretation of this observation are discussed in more detail below. 

Fig. 3. Linear correlation of AH0 versus ACp at 25°C for protein denaturation for the proteins listed in Table IV. (a) Normalized per number of residues (b) normalized per total buried area. The line in (a) is the linear regression fit with a slope of — 72.4 corresponding to a convergence temperature of 97.4°C. The line in (b) represents the line calculated from the parameters in Table II for convergence at the temperature at which the polar and apolar contributions to AH are equal per unit area. See text for details.

Comparison of results on thermodynamic studies of protein denaturation and hydrocarbon dissolution in water shows a number of surprising similarities and differences between these two processes. The most surprising result is the close correspondence of the temperature of convergence of the enthalpy and entropy functions for the denaturation of proteins, Tx, and the temperature 7s for the dissolution of hydrocarbons in water. 

Privalov et al. (1989) also reported the temperature dependence of the ellipticity at 222 nm for the proteins studied at various pH values (Fig. 28). At the highest temperature studied (80°C), the 222 nm ellipticity value for the thermally unfolded, acid-unfolded, and Gdm-HCl-unfolded proteins appear to be converging, but show a range of 2000 deg cm2/dmol out of a total of 5000 deg cm2/dmol. (ApoMb is an exception in that, as noted before, the thermally denatured protein is apparently an associated /1-sheet. However, the acid- and Gdm HC1-unfolded forms of apoMb have similar [0] 222 values at 80°C.)... 

The simplicity and accuracy of such models for the hydration of small molecule solutes has been surprising, as well as extensively scrutinized (Pratt, 2002). In the context of biophysical applications, these models can be viewed as providing a basis for considering specific physical mechanisms that contribute to hydrophobicity in more complex systems. For example, a natural explanation of entropy convergence in the temperature dependence of hydrophobic hydration and the heat denaturation of proteins emerges from this model (Garde et al., 1996), as well as a mechanistic description of the pressure dependence of hydrophobic... 

One of the key observations resulting from calorimetric studies of the denaturation of globular proteins is that both AH0 and AS0 of denaturation, when normalized to the number of amino acid residues in the protein (or the molecular weight), converge to common values at specific temperatures when extrapolated under the assumption of constant ACp (Privalov and Khechinashvili, 1974 Privalov, 1979 Pri-... 

The general thermodynamic properties of proteins reported above give rise to several questions What do the asymptotic (at Tx) values of the denaturation enthalpy and entropy mean and why are they apparently universal for very different proteins Why should the denaturation enthalpy and entropy depend so much on temperature and consequently have negative values at low temperature In other words, why is the denaturation increment of the protein heat capacity so large, with a value such that the specific enthalpies and entropies of various proteins converge to the same values at high temperature ... 

It was suggested earlier that hydrogen bonds in proteins are the main contributors to the denaturation enthalpy at 7X, whereas the nonpolar contacts determine only the temperature dependence of the denaturation enthalpy (Privalov, 1979). The main argument for this was the observation that proteins that have the same enthalpies at Tx have an almost equal concentration of intramolecular hydrogen bonds, but differ in the concentration of nonpolar contacts (Table I). As is evident, the assumption of the dominant role of hydrogen bonds in the stabilization of protein structure explained the observed temperature convergence of the denaturation enthalpy, if the enthalpy of exposure of nonpolar groups to water is zero at this temperature. This assumption implied that either the enthalpy of... 

A typical stability curve and the fractional population sizes are shown in Figure 2. It is worth noting that according to equation 16 the fractions of both the native and denatured proteins converge to zero, but never reach it. Therefore the statement at physiological temperatures the protein is in the native state must be interpreted more precisely as meaning that at physiological temperatures the native state is predominant . 

---