Solution properties of γ-crystallins: compact structure and low frictional ratio are conserved properties of diverse γ-crystallins.

γ-crystallins are highly specialized proteins of the vertebrate eye lens where they survive without turnover under high molecular crowding while maintaining transparency. They share a tightly folded structural template but there are striking differences among species. Their amino acid compositions are unusual. Even in mammals, γ-crystallins have high contents of sulfur-containing methionine and cysteine, but this reaches extremes in fish γM-crystallins with up to 15% Met. In addition, fish γM-crystallins do not conserve the paired tryptophan residues found in each domain in mammalian γ-crystallins and in the related β-crystallins. To gain insight into important, evolutionarily conserved properties and functionality of γ-crystallins, zebrafish (Danio rerio) γM2b and γM7 were compared with mouse γS and human γD. For all four proteins, far UV CD spectra showed the expected β-sheet secondary structure. Like the mammalian proteins, γM7 was highly soluble but γM2b was much less so. The heat and denaturant stability of both fish proteins was lower than either mammalian protein. The ability of full-length and truncated versions of human αB-crystallin to retard aggregation of the heat denatured proteins also showed differences. However, when solution behavior was investigated by sedimentation velocity experiments, the diverse γ-crystallins showed remarkably similar hydrodynamic properties with low frictional ratios and partial specific volumes. The solution behavior of γ-crystallins, with highly compact structures suited for the densely packed environment of the lens, seems to be highly conserved and appears largely independent of amino acid composition.