ELECTROSTATIC PARAMETERS OF THE THEORETICAL QUATERNARY STRUCTURE OF BOVINE ALPHA-CRYSTALLIN

By changing the ionic strength, the effects of charge modification on the electrostatic properties of our predicted 'open' micellar quaterna ry structure composed of bovine alpha A subunits were determined. The electrostatic potential values (phi) at 6 arbitrary points surrounding the protein and at all atomic sites of the protein were calculated us ing the non-linear Poisson-Boltzmann equation. The effective charge (q ) of our predicted aggregate ranged from 16 at 0.0022 M to 45 at 0.147 2 M ionic strengths. The variation of potential (phi), as well as char ge, is a hyperbolic function of ionic strength (R(2), 0.901). Plotting the inverse charge (1/q) against inverse ionic strength (1/I) it is p ossible to calculate maximum charge (q(max)) (similar to 48) at satura tion. This value is close to previously reported experimental (50 +/- 5), and our theoretical charge (45), values at physiological ionic str ength (0.145 M). These data indicate that maximal repulsion among the alpha-crystallin aggregates occurs at or near physiological ionic stre ngth, Also, half-maximal charge (q(max)/2) at 0.003-0.004 M indicates a transition state at very low ionic strength. The calculated volume a vailable for the mobile solvent in our quaternary structure is similar to 70%, These data are in good agreement with experimental values for bovine alpha-crystallin in solution reported by Xia et al. (Biophys. J., 1994; 66: 861-872). This agreement provides support for our predic ted models of alpha-crystallin and a level of confidence in the reliab ility of the theoretical calculations. Since an ionic gradient exists between the lens cortical and nuclear regions, the modification of cha rge on alpha-crystallin by varying ionic strength could contribute to the function of alpha-crystallin as a modulator of lens supermolecular order during fiber cell maturation.