Globular proteins transition

Privalov, P.L., N.N. Khechinashvili, and B.P. Atanasov. 1971. Thermodynamic analysis of thermal transitions in globular proteins. I. Calorimetric study of chy-motrypsinogen, ribonuclease and myoglobin. Biopolymers 10 1865-1890. 

Ptitsyn, O. B., A. K. Kron, and Yu. E. Eizner The models of the denatura-tion of globular proteins. I. Theory of globule-coil transitions in macromolecules. IUPAC Symposium on Macromolecular Chemistry, Prague 1965, Preprint 474. 

Both the denaturation process in proteins and the melting transition (also referred to as the helix-to-coil transition) in nucleic acids have been modeled as a two-state transition, often referred to as the all-or-none or cooperative model. That is, the protein exists either in a completely folded or completely unfolded state, and the nucleic acid exists either as a fully ordered duplex or a fully dissociated monoplex. In both systems, the conformational flexibility, particularly in the high-temperature form, is great, so that numerous microstates associated with different conformers of the biopolymer are expected. However, the distinctions between the microstates are ignored and only the macrostates described earlier are considered. For small globular proteins and for some nucleic acid dissociation processes,11 the equilibrium between the two states can be represented as... 

In all globular proteins studied, a significant increase in the heat capacity of the denatured protein relative to the native state has been observed in the vicinity of the denaturation transition. (This quantity is represented in... 

Indeed, since the macroscopic states of a protein are discrete, they are described by discrete surfaces in the phase space of considered variables (Pfeil and Privalov, 1976c). The small globular proteins, or individual cooperative domains, which have only two stable macroscopic states, the native (N) and denatured (D), are described by two surfaces in the phase space, corresponding to their extensive thermodynamic functions. The transition between these states is determined by the differences of... 

The Gibbs energy difference of the denatured and native states corresponds to the work required for the transition of a system from the native to the denatured state, i.e., the work of disruption of the native cooperative structure. Therefore, this quantity is usually considered as a measure of the stability of the cooperative structure, i.e., the stability of a small globular protein or cooperative domain. As for the large proteins, their stability cannot be expressed by a single value, but only by a set of values specifying the stability for each domain within these molecules and the interaction between the domains. 

The specific enthalpy and entropy of the conformation transition of proteins from the native to denatured state has an upper limit that is reached above 140°C and seems to be universal for all compact globular proteins (Figs. 4 and S). By enthalpy and entropy of conformational tran-... 

For compact proteins with molecular masses of greater than 10,000 and saturation of native structure by intramolecular hydrogen bonds of about 0.75 0.10 mole of bonds per mole of amino acid residues, the asymptotic values of enthalpy and entropy of the conformational transition, calculated per amino acid residue, amount to A%H(TX) = (6.25 0.2) kJ mol-1 and A 5(7 x) = (17.6 0.6) J K-1 mol-1. For some noncompact proteins (e.g., histones) or small globular proteins with molecular masses... 

At this temperature, the entropy change for dissolution of liquid hydrocarbons in water is zero. However, the entropy of protein denaturation is far from zero at this temperature but amounts to 17.6 J - K l per mole of amino acid residues (Privalov, 1979), a value that corresponds to an 8-fold increase of the number of possible configurations and is close to the value expected for the helix-coil transition of polypeptides (Schellman, 1955). This difference shows that an oil drop is an inadequate model for a globular protein. A more suitable model resembles that of a small crystal with a quite definite positive melting entropy (see also Bellow, 1977, 1978). 

Go N, Abe H (1981) Noninteracting local-structure model of folding and unfolding transition in globular proteins. I. formulation, Biopolymers 20 991-1011... 

M. Vasquez, M. R. Pincus, and H. A. Scheraga, Biopolymers, 26, 351 (1987). Helix-Coil Transition Theory Including Long-Range Electrostatic Interactions Application to Globular Proteins. 

This behavior can be seen as complementary to another aspect of protein folding the withdrawal of hydrophobic side chains from solvent. The latter minimizes perturbation by burying those portions of the polypeptide for which water is the poorest solvent. The former minimizes perturbation of solvent by what remains exposed. Not all biological macromolecules show so small an effect. Nucleic acids require for their hydration about twice the amount of water required by globular proteins (for heat capacity measurements comparing protein and tRNA, see Rupley and Siemankowski, 1986). It may be signihcant that DNA, with an extensive hydration shell, undergoes facile hydration-dependent conformational transitions, which are not found for proteins. 

The initial decrease in optical rotation found in aqueous solutions of /3-lactoglobulin and ovalbumin is not, however, sufficient to differentiate globular proteins from simpler synthetic polypeptides in their transition behavior, for neither ribonuclease nor human serum albumin appear to exhibit it. The specific rotation of ribonuclease in water-2-chloroethanol mixtures becomes steadily less levorotatory as the proportion of nonpolar solvent increases (Weber and Tanford, 1959). In the case of human serum albumin Bresler (1958) and Bresler el al. (1959) find that only progre.ssive increases in specific rotation occur as the concentration of 2-chloroethanol is increased and that this change is accompanied by a steady rise in viscosity and the corresponding axial ratios characteristic of the formation of rodlike particles. If these proteins do have some initial helical content in water, as can be argued from their optical rotatory dispersion, then it appears that hydrophobic forces are not required for the stability of these regions. 

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