Effect on protein folding

Protein glycosylation is a PTM of eukaryotic proteins and does not occur in prokaryotes. The carbohydrate groups are highly variable with significant effects on protein folding, stability, and activity. The importance of HPCE for the analysis of glycosylated proteins is described in Chapter 22. 

Cold denaturation is an interesting phenomenon that results from hydration of polar and nonpolar proteins and weakening of hydrophobic forces, all of which have a significant effect on protein folding and stability. Intracellular enzymes from psychrophiles are protected from cold denaturation by compatible solutes, such as potassium glutamate and trehalose (67). Psychrophiles also have intracellular cold shock proteins that act as chaperones, cryoprotectors, and antifreeze molecules. There is no explanation yet for protection from cold denaturation for extracellular psychrophilic enzymes, but exopolymeric substances may be involved (67). 

H Taketomi, Y Ueda, N Go. Studies on protein folding, unfolding and fluctuations by computer simulation. 1. The effect of specific ammo acid sequence represented by specific mter-umt interactions. Int J Peptide Protein Res 7 445-459, 1975. 

The van der Waals model of monomeric insulin (1) once again shows the wedge-shaped tertiary structure formed by the two chains together. In the second model (3, bottom), the side chains of polar amino acids are shown in blue, while apolar residues are yellow or pink. This model emphasizes the importance of the hydrophobic effect for protein folding (see p. 74). In insulin as well, most hydrophobic side chains are located on the inside of the molecule, while the hydrophilic residues are located on the surface. Apparently in contradiction to this rule, several apolar side chains (pink) are found on the surface. However, all of these residues are involved in hydrophobic interactions that stabilize the dimeric and hexameric forms of insulin. 

Litowski, J. R., and Hodges, R. S. (2001). Designing heterodimeric two-stranded alpha-helical coiled-coils The effect of chain length on protein folding, stability and specificity./. Pept. Res. 58, 477-492. 

How then can we account for the high degree of internal order routinely found within globular proteins We believe that combinations of the wide variety of electrostatic interactions reviewed above determine the precise three-dimensional structure of the interior of a protein. We argue that the sum of these interactions produces, at least in part, the enthalpy change on protein folding that is independent of the hydrophobic effect. Crystal structures of small organic compounds provide a useful model of protein interiors, and we now discuss some recent theoretical studies of these systems. 

The redox potential of the bacterial cell is of a reducing nature compared to that in the eukaryotic cytoplasm. This has a negative effect on the folding of eukaryotic proteins... 

Singer, M.A., and S. Lindquist (1998b). Multiple effects of trehalose on protein folding in vitro and in vivo. Mol. Cell 1 639-648. 

Stellacyanin is also an important example of a heavily glycosylated protein for which the structure has been determined without its glyco components. It demonstrated that the carbohydrate moieties have virtually no effect on the folding topology of the polypeptide core of this particular glycoprotein. One of the three glycosylation sites in... 

Nearest-neighbor effects refer to the reciprocal influence of adjacent amino acids on protein folding. In some cases, this term also refers to amino acids that are close in the 3-D structure of the protein (<8-10 A away), but distant in the sequence. Early studies found a nonrandom assorting of amino acids in secondary structures by pair-wise analysis of protein sequences (43). More recently, it was reported that the preference of pairs of amino acids for secondary structure was determined, in part. 

Levitt, M. Effect of proline residues on protein folding. J. Molec. Biol. 145. 251-263 (1981). 

Shental-Bechor, D., Levy, Y. Effect of glycosylation on protein folding A close look at thermodynamic stabilization. Proc. Natl. Acad. Sci. U.S.A. 2008,105, 8256-61. 

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