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. 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. We have developed new protocols for production of endotoxin-free gS and mutant gS for collaborative experiments Structural work has identified a key conserved residue in gS-crystallin that seems to be important for certain intermolecular interactions. Screenings have identified conditions for crystallization of gS in a novel complex. We have created a mouse line in which this residue is mutated to analyze the consequences for retina and lens function. CryoEM studies of lengsin and its intermediate filament binding proteins are nearing solution. A high resolution structure of lengsin has been obtained. Analysis of the complex with the 2B fragment of CP49 is in progress.