Structural Basis for Extreme Cold Stability in the Eye Lenses of Teleost Fishes

Chi-Hing Cheng, University of Illinois at Urbana-Champaign

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Eye lenses of endothermic mammals such as the cow develop cold cataract at ~17°C. In contrast, ectothermic teleost fish lenses remain transparent down to -12°C. Cold induced cataract arises from a liquid-liquid phase-separation of lens proteins (crystallins) resulting in a protein-rich and a protein-poor phase. Crystallins are tightly packed at high concentrations to enable refraction of incident light, and teleost lenses are especially protein dense to achieve a refractive index change in aquatic environments. We propose that teleost crystallins are structurally more flexible than mammalian isoforms to minimize the propensity of phase separation at their very high concentrations, conferring the observed stability at very low temperatures as a side benefit. Preliminary molecular dynamics (MD) simulations on a subset of γ-crystallin isoforms from teleost fishes and mammals at normal and cold temperatures lend support to our hypothesis. The large number of γ-crystallin simulations remaining require the computational capacity of the petascale Blue Waters. The results of the study will provide insights into the structural mechanisms underlying the intriguing extreme cold-stability of the teleost eye lens.