Protein preferential interaction

There are two main mechanisms of solvent-induced stabilization of proteins (i) strengthening of the protein-stabilizing forces or (ii) destabilization of the denatured state (18). The most tenable and widely accepted mechanism of protein stabilization in aqueous solution is the preferential interaction of proteins. Preferential interaction indicates that a protein prefers to interact with either water or the excipient. The two conventionally applied terms are preferential hydration, which means that a protein prefers to interact with water, or preferential exclusion, which means that for example the excipient is... 

The specific protein-DNA interactions described in this book are all with DNA in its regular B-form, or, in some cases with distorted B-DNA. In biological systems DNA appears not to adopt the A conformation, although double-stranded RNA does preferentially adopt this conformation in vivo. Whether or not Z-DNA occurs in nature is a matter of controversy. However, the formation of A-DNA and Z-DNA in vitro does illustrate the large structural changes that DNA can be forced to undergo. 

Timasheff, S.N. (1982). Preferential interactions in protein-water-cosolvent systems. In Biophysics of Water, ed. F. Franks, pp. 70-2. London John Wiley. 

Separations in hydrophobic interaction chromatography have been modeled as a function of the ionic strength of the buffer and of the hydrophobicity of the column, and tested using the elution of lysozyme and ovalbumin from octyl-, butyl- and phenyl-Sepharose phases.2 The theoretical framework used preferential interaction analysis, a theory competitive to solvophobic theory. Solvophobic theory views protein-surface interaction as a two-step process. In this model, the protein appears in a cavity in the water formed above the adsorption site and then adsorbs to the phase, with the free energy change... 

The nucleosome core particle is a relatively stable and homogenous structure that is easily prepared, and as such has formed the basis for numerous studies into chromatin structure and function. However, several recent studies have suggested that what is true for the nucleosome core may not always be true for nucleosome arrays, nor even for nucleosomes containing linker DNA. For example, the core histone tails preferentially interact with linker DNA when is it present, whereas they are constrained to bind intranucleosomal DNA in core particles [46 8]. Consequently, the activities of proteins that require access to the tails or the DNA may be affected, and it has been shown that both DNA ligase and P/CAF are less active on nucleosome core particles than other chromatin substrates [49,50]. Similar concerns apply to the interaction of HMGN proteins with nucleosome core particles, and results from studies of these complexes must be considered in the wider context of how these proteins may interact with nucleosome arrays. 

Extensive literature has developed related to the preferential interaction of different solvents with proteins or peptides in bulk solution.156-5X1 Similar concepts can be incorporated into descriptions of the RPC behavior of peptides and employed as part of the selection criteria for optimizing the separation of a particular peptide mixture. As noted previously, the dependency of the equilibrium association constant, /CassoCji, of a peptide and the concentration of the solvent required for desorption in RPC can be empirically described1441 in terms of nonmechanistic, stoichiometric solvent displacement or preferential hydration models, whereby the mass distribution of a peptide P, with n nonpolar ligands, each of which is solvated with solvent molecules Da is given by the following ... 

Arakawa T, Timasheff SN. Preferential interactions of proteins with solvent components in aqueous amino acid solutions. Arch Biochem Biophys 1983 24(1) 169-177. 

While applicability of Equation 4 requires that all measurements be done at constant pressure, in practice it is much simpler to do the measurements in a state of dialysis equilibrium—i.e., at constant T, p, and /xi. The error introduced by the practical approximation (dmi/dm2)T,p,m = (dmo)T,p.o.m is minor (16). In this manner, light-scattering measurements on protein solutions in a mixed solvent, with and without dialysis, make possible the determination of both the molecular weight and the extent of preferential interaction of the protein with one of the solvent components (21). 

Lactoglobulin A in 40% 2-Chloroethanol. Previous light scattering and differential refractometry measurements (8, 23) have shown that / -lactoglobulin exhibits strong preferential interactions with solvent components in the water-2-chloroethanol system. Since the preferential interaction between protein and 2-chloroethanol in this system was found to be maximal at 40% (v/v), the effect of this interaction on the partial specific volume of the protein was determined. 

In a mixed solvent system a macromolecule may display an overall preferential interaction for one of the solvent components, but this does not eliminate interactions with the other solvent component as well. For example, in the water-2-chloroethanol system, particular regions of the protein molecule, such as ionized side chains, must be interacting with water molecules. Therefore, the extent of preferential interaction observed must be related to the absolute interactions of the protein with the solvent components. In fact, it can be shown (40) that ... 

Figure 1. Schematic of preferential interactions. P protein W water D denaturant.

T. Arakawa, S. N. Timasheff, Preferential interactions of proteins with salts in concentrated solutions, Biochemistry 1982b, 21, 6545-6552. 

Fig. 3. Two-dimensional analysis of PDZ proteins interacting with the 5-HT2A and the 5-HT2C receptors C-termini. (A) Proteins from mice brain that bind to the C-terminus of the last 14 residues of the receptors were separated on 2D gels and stained with silver. Proteins that interact specifically (directly or indirectly) with the PDZ ligand of the receptor (arrows) were detected comparing protein patterns obtained with the native peptides (see Fig. 1) and mutant peptides in which the last residue was replaced by alanine. The position of one protein retained in a PDZ-independent manner by the 5-HT2A receptor C-terminus is also indicated (arrowhead). (B) Molecular determinants in the C-terminus of 5-HT2A receptor involved in its preferential interaction with CIPP.

The addition of polyhydroxyl compounds to enzyme solutions have been shown to increase the stabilities of enzymes, (13,16,19,20). This is thought to be due to the interaction of the polyhydroxyl compound, (e.g. sucrose, polyethylene glycols, sugar alcohols, etc), with water in the system. This effectively reduces the protein - water interactions as the polyhydroxy compounds become preferentially hydrated and thus die hydrophobic interactions of the protein structure are effectively strengthened. This leads to an increased resistance to thermal denaturadon of the protein structure, and in the case of enzymes, an increase in the stability of the enzyme, shown by retention of enzymic activity at temperatures at which unmodified aqueous enzyme solutions are deactivated. 

Table 8-1. Structures of LAP inhibitors, phosphinate dipeptide analogues, designed using LUDI. Experimental and predicted activities are presented for each compounds. a Value corresponding to the mixture of two diastereomers (1 1). Binding affinity for the mixture of four diastereomers. Value corresponding to the racemic mixture. Predicted binding affinity for one isomer which preferentially interacts with the protein...

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