γ-Crystallins constitute the major protein component in the nucleus of the vertebrate eye lens. Present at very high concentrations, they exhibit extreme solubility and thermodynamic stability to prevent scattering of light and formation of cataracts. However, functions beyond this structural role have remained mostly unclear. Here, we calculate molecular refractive index increments of crystallins. We show that all lens γ-crystallins have evolved a significantly elevated molecular refractive index increment, which is far above those of most proteins, including nonlens members of the βγ-crystallin family from different species. The same trait has evolved in parallel in crystallins of different phyla, including S-crystallins of cephalopods. A high refractive index increment can lower the crystallin concentration required to achieve a suitable refractive power of the lens and thereby reduce their propensity to aggregate and form cataracts. To produce a significant increase in the refractive index increment, a substantial global shift in amino acid composition is required, which can naturally explain the highly unusual amino acid composition of γ-crystallins and their functional homologues. This function provides a new perspective for interpreting their molecular structure.
Copyright © 2011. Published by Elsevier Ltd.