Ribonuclease hydrophobic regions

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. 

The proposed interactions in ribonuclease are represented schematically in Fig. 167. The circled regions in forms I, II, and HI indicate an interaction between a tyrosyl and a carboxyl group (surrounded by hydrophobic groups). The uncircled carboxyl group in form I is also involved in some... 

While hydrophobicity is (whatever its origin) certainly an important force that guides the recognition of a protein and its substrate, water seems also to be important for the interaction of hydrophilic regions of such complexes. Around 70% of interfacial residues are in fact hydrophilic. It is common to assume that such polar groups experience a direct electrostatic interaction mediated by the (continuum) solvent. But in fact the water network has a more complex role here too. For example, in the formation of the complex between the bacterial ribonuclease bamase and its inhibitor barstar, water molecules mediate and stabilize the hydrophilic interactions between receptor and substrate at the granular level [60]. 

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