Molecular Structure and Function of Crystallins

National Eye Institute

Investigators

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Abstract

gamma-Crystallins are associated with cataract in both human and animal models. They may also have stress related roles in other eye tissues, notably retina. We have shown that they can play a role in stabilization of cytoskeleton in lens. We have identified an unexpected mode of dimerization in many g-crystallins that correlates with the magnitude and direction of molecular dipoles. AUC data with our collaborators show that gS-crystallins do dimerize at high concentrations similar to those found in the lens. We have also shown how g-crystallins can undergo structural changes that may contribute to aggregation and cataract. g=Crystallins are also expressed in retina. Deletion of the CRYGS gene in mouse leads to age-related defects including swelling in the GCL and alterations in retinal vasculature, similar to some age-related diseases. We are also collaborating on unexpected observations that CRYGS plays a role in inflammatory responses in retina. Structural work has identified a key conserved residue in gS-crystallin that seems to be important for certain intermolecular interactions. We have created a mouse line in which this residue is mutated and are beginning to analyze the consequences for retina and lens function.