Protein structure stability

Burley SK, Petsko GA. Aromatic-aromatic interactions a mechanism of protein structure stabilization. Science 1985 229 23-28. 

Pace CN, Trevino S, Prabhakaran E, et al. Protein structure, stability and solubility in water and other solvents. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 2004 359 1225-1235. 

The sorbent materials are supplied as finely dispersed colloidal particles, whose surfaces are smooth. Some of their properties are presented in Table 3. The sorbents cover different combinations of hydrophobicity and sign of the surface charge. Thus, the model systems presented allow systematic investigation of the influences of hydrophobicity, electric charge, and protein structural stability on protein adsorption. 

Stability of an enzyme is usually understood to mean temperature stability, although inhibitors, oxygen, an unsuitable pH value, or other factors such as mechanical stress or shear can decisively influence stability (Chapter 17). The thermal stability of a protein, often employed in protein biochemistry, is characterized by the melting temperature Tm, the temperature at which a protein in equilibrium between native (N) and unfolded (U) species, N U, is half unfolded (Chapter 17, Section 17.2). The melting temperature of a protein is influenced on one hand by its amino acid sequence and the number of disulfide bridges and salt pairs, and on the other hand by solvent, added salt type, and added salt concentration. Protein structural stability was found to correlate also with the Hofmeister series (Chapter 3, Section 3.4 Hofmeister, 1888 von Hippel, 1964 Kaushik, 1999) [Eq. (2.18)]. 

Murphy, K. P., Ed. (2001) Protein Structure, Stability and Folding. Humana Press, Totowa, NJ. 

We review the subject of noncovalent interactions in proteins with particular emphasis on the so-called weakly polar interactions. First, the physical bases of the noncovalent electrostatic interactions that stabilize protein structure are discussed. Second, the four types of weakly polar interactions that have been shown to occur in proteins are described with reference to some biologically significant examples of protein structure stabilization and protein-ligand binding. Third, hydrophobic effects in proteins are discussed. Fourth, an hypothesis regarding the biological importance of the weakly polar interaction is advanced. Finally, we propose adoption of a systematic classification of electrostatic interactions in proteins. 

Directed evolution as a tool to probe the basis of protein structure, stability, and function is in its infancy, and many fruitful avenues of research remain to be explored. Studies so far have focused on proteins that unfold irreversibly, making detailed thermodynamic analysis impossible. The application of these methods to reversibly folding proteins could provide a wealth of information on the thermodynamic basis of high temperature stability. A small number of studies on natural thermophilic proteins have identified various thermodynamic strategies for stabilization. Laboratory evolution makes it possible to ask, for example, whether proteins have adopted these different strategies by chance, or whether certain protein architectures favor specific thermodynamic mechanisms. It will also be possible to determine how other selective pressures, such as the requirement for efficient low temperature activity, influence stabilization mechanisms. The combination of directed evolu-... 

Izutsu K-I, Kojima S. Excipient crystallinity and its protein-structure-stabilizing effect during freeze-drying. / Pharm Pharmacol 2002 54 1033-1039. 

Aromatic-aromatic stacking interactions are significant contributors to protein structure stabilization (Burley and Petsko 1985). Modeling studies indicate that in the active state (R ) model of CBi, there is a patch of aromatic amino acids in the TMH 3-4-5 region with which WIN 55,212-2 can interact (McAllister et al. 2003). There is an upper (extracellular side) stack formed by F3.25(189 in human CBi, 190 in mouse CBi), W4.64(255/256), 5.39(275/276), and W5.43(279/280). When WIN 55,212-2 is computationally docked to interact with this patch, it also can interact with a lower (towards intracellular side) aromatic residue, F3.36(200/201). In this docking position, WIN 55,212-2 creates a continuous aromatic stack over... 

Electrostatic interactions play an important role in many aspects of biology, such as protein structural stability, enzyme function, gene expression, ion transport, and protein-protein interactions. Consequently, the number of publications studying these interactions continues to grow every year. Continuum methods are by far the most common approach to studying electrostatic interactions. In continuum methods, the solute is usually represented as a... 

Protein Structure, Stability, and Folding, edited by Kenneth P. Murphy, 2001... 

Burley, S. K., and Petsko, G. A. (1985). Aromatic-aromatic interaction A mechanism of protein structure stabilization, Sc/ence 229, pp. 23-28. 

Pace, C. N., S. Trevino, E. Prahhakaran, and J. M. Seholtz. 2004. Protein structure, stability and soluhihty in water and other solvents. Philosophical Transactions of the Royal Society of London Series B-Biological Sciences. 359,1225. 

FIGURE 13.2 Gibbs energy landscape of protein structure stability. (Adapted from Dill, K.A. and Chan, H.S., Nat. Struct. Biol., 4, 10, 1997.)... 

The most detailed thermodynamic analysis of protein structure stability is based on differential scanning calorimetry (DSC). In a DSC experiment, the heat capacity Cp of a sample is monitored while heating (or cooling) the sample. Figure 13.13 shows a typical DSC thermogram for heat-induced denaturation of a protein in solution. The thermodynamic observables are the temperature of denaturation (the temperature at half-peak area), the enthalpy change An, d (T involved in the denaturation process (the area under the peak), and the change in the heat capacity A,, dC of the solution (the shift of the baseline). 

If the protein molecule and the surface are polar, it is probable that some hydration water is retained between the surface and the adsorbed protein layer. However, if (one oO the surfaces are (is) apolar, dehydration would be a driving force for adsorption. Although the apolar residues of a globular protein in water tend to be buried in the interior of the molecule, the water accessible surface of the protein may still comprise a significant apolar fraction, even up to 40%-50% (cf. Section 13.2). In this context it should be realized that apart from the polarity of the outer shell the overall polarity of the protein could be relevant for its adsorption behavior. The overall polarity influences the protein structural stability (cf. Section 13.3) and, hence, the extent of structural perturbation upon adsorption. This, in turn, affects the adsorption affinity, as discussed in the following section. 

---