Molecular Chaperone Function of Site-Directed Mutants of αA- and αB-Crystallins

Abstract

(Statement of the Problem) Cataract formation causes blindness in more than 17 million people worldwide (1). The only treatment present to date is lens surgery. The magnitude of this problem and the limitations o f cataract surgery have stimulated research in animals as well as in vitro studies and epidemiological studies. Research in this field is directed towards preventing or at least delaying cataract development. A thorough understanding of the process of cataractogenesis and the mechanisms involved is essential for the advancement in this area. a-Crystallin, a major lens protein belonging to the heat-shock protein family, play a role in maintaining lens transparency because of its ability to function as a chaperone, (i.e. having the ability to suppress aggregation o f other lens proteins which cause lens opacity). Oxidative modifications and hydrophobic interactions of certain amino acid residues could affect the chaperone function of a-crystallin. Congenital cataracts are a major cause of blindness in infants and some are due to mutations occurring in crystallins including a-crystallin. The current study investigated the impact of three types o f modifications on the chaperone-like function of a-crystallin. The modifications were 1) oxidation, 2) the presence of specific hydrophobic or hydrophilic amino acid residues and 3) a mutation which has been identified as the cause of an autosomal congenital cataract in humans.