gamma-crystallins are associated with cataract in both human and animal models. To explore the functional characteristics of g-crystallins, proteins from fish and birds representing the extremes of the family in composition and behavior have been expressed. Using recombinant g-crystallins in several biophysical studies, we have shown that they have highly unusual solution properties that fit them for high protein concentration environments and shed light on how they unfold under stress. Studies on chicken gS-crystallin show how a single amino acid change in ancient ancestors of birds significantly affecetd the structure and stability of the protein. This protein also exhibits remarkable properties in solution that suggest it may be a model for a stage in the process of unfolding. This and other work is shedding light on the processes of unfolding and amyloid formation involving crystallins and the also the protective, chaperone role of a-crystallin. This has wider significance for understanding how normally folded proteins can unfold and adopt other structures that can have serious consequences for cellular function. Detailed NMR structure analysis has been used to determine the first structure of gM7-crystallin from zebrafish, representing an extreme member of the family in terms of composition and behavior. The structure is generally well-conserved but illustrates some specific changes resulting from replacement of key residues that show how those residues contribute to the tightly folded structure of human gamma-crystallins.
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