Proctor Lecture. The function of alpha-crystallin.

L he term "crystallin" applies to the major structural proteins responsible for the refractive properties of the lens." The crystallins generally make up 90% or more of the total protein mass. The crystallins are tightly packed in the lens fiber cells (Fig. 1). In vertebrates, the most common crystallins are the a, /3, and y families. In birds and reptiles, there is another major lens protein, called the 5-crystallin. In recent years, many other crystallins have been identified in various species; these have been named taxon-specific crystallins". The great advances in protein and DNA sequencing in the past two decades, coupled with the availability of powerful computer systems for sequence analysis, have produced many surprises regarding the origin and properties of the lens crystallin. In 1982, Ingolia and Craig showed that mammalian a-crystallin is related to a family of small heat shock proteins in Drosophila. Sequence analysis of the taxon-specific crystallins showed them to be related or identical to various metabolic enzymes. For example, duck €-crystallin is identical to lactate dehydrogenase B4; 5-crystallin is related to a urea cycle enzyme, argininosuccinate lyase; and r-crystallin is related to a-enolase. Even lenses in the complex eyes of invertebrates have major structural proteins related to metabolic enzymes. For example, cephalopod crystallins are derived from glutathione-S-transferase and aldehyde dehydrogenase. These findings suggest that lens crystallins were recruited from functional enzymes to serve as structural proteins, hence the name "enzyme-crystallins."Interestingly, in some cases, such as <5, e, and r, these recruited crystallins retained their enzymic activity. The dual function of these proteins, which can serve as structural proteins or enzymes, led