Tissues of the eye depend on families of specialized proteins. In the lens, the major proteins the crystallins. We have shown that in humans and other species, crystallins have arisen by a process called Gene Recruitement. Proteins such as enzymes and stress proteins have been recruited to serve an additionl structural role in lens transparency. The origins and functions of many classes of crystallins have been elucidated. Currently we are investigating the last major group for which a function is unknown. These are the related beta(b) and gamma (g) crystallins. Non-lens relatives of these proteins with stress and cancer related functions have been identified. This includes a novel gene expressed in human retinal pigment epithelium. We have also shown that gS crystallin and bA2 crystallin have non-lens expression possibly relecting a non-lens function. The genes for both these proteins have been sequenced. We have shown that gS is the locus of the Opj cataract in mouse and have evidence for loss of function in control of fiber cell structure. Recombinant wild type and mutant proteins for gS have been produced for functional studies. The mutant protein in Opj contains a temperature-sensitive destablizing mutation. Around mouse body temperature one domain unfolds and causes the protein to become insoluble. In some species enzymes have been recruited as crystallins. We have produced recombinant protein for one of these, eta-crystallin, which is a retinaldehyde dehydrogenase. A crystal structure has been determined in collaboration with the Birkbeck College group. We have also expressed mu-crystallin, an enzyme of unknown function but probably involved in unusual amino-acid metabolism which is also implicated in some human diseases.
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