Crystal Structure of Chicken γS-Crystallin Reveals Lattice Contacts with Implications for Function in the Lens and the Evolution of the βγ-Crystallins

Previous attempts to crystallize mammalian γS-crystallin were unsuccessful. Native L16 chicken γS crystallized avidly while the Q16 mutant did not. The X-ray structure for chicken γS at 2.3 Å resolution shows the canonical structure of the superfamily plus a well-ordered N arm aligned with a β sheet of a neighboring N domain. L16 is also in a lattice contact, partially shielded from solvent. Unexpectedly, the major lattice contact matches a conserved interface (QR) in the multimeric β-crystallins. QR shows little conservation of residue contacts, except for one between symmetry-related tyrosines, but molecular dipoles for the proteins with QR show striking similarities while other γ-crystallins differ. In γS, QR has few hydrophobic contacts and features a thin layer of tightly bound water. The free energy of QR is slightly repulsive and analytical ultracentrifugation confirms no dimerization in solution. The lattice contacts suggest how γ-crystallins allow close packing without aggregation in the crowded environment of the lens. [Display omitted] •Crystal structure of γS-crystallin sheds light on contacts in the crowded eye lens•Monomeric γS forms a non-bonding lattice contact like dimeric β-crystallins•Common interface conserves orientation but only one conserved side-chain contact•Common interface is associated with similar patterns of molecular dipoles The crystal structure of γS-crystallin shows how proteins in the eye lens can form non-binding contacts with low hydration without aggregation. Monomeric γS also forms an intermolecular interface very similar to one in dimeric β-crystallins: few contacts are conserved but molecular dipoles have similarities.