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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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Chi-Hing Cheng, Michael Grispo

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 paralogs, preventing aggregation and lending to protein stability at low temperatures as a side benefit. To test our structural flexibility hypothesis, we will conduct molecular dynamics (MD) simulations to compare a large set of γ-crystallin isoforms from teleost fishes and mammals at normal and cold temperatures. The large number of γ-crystallins 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.