[alpha]A-crystallin derived peptide, [alpha]A66-80 induced aggregation and precipitation of soluble [alpha]-crystallin : a contribution to age-related cataract formation
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Age-related cataract is the result of aggregation of lens proteins, crystallins. The formation of aggregates in the aging lens has been shown to correlate with progressive accumulation of specific low molecular weight (LMW) peptides (<3.5-kDa) derived from crystallins. Prominent among LMW peptides is [alpha]A66-80, a peptide derived from [alpha]A-crystallin and present in increased concentrations in the water-insoluble fractions of the aging lens. We investigated the characteristics of the peptide and its interactions with soluble [alpha]-crystallin. The [alpha]A66-80 peptide has amyloid-like properties and preferentially insolubilizes [alpha]-crystallin from soluble lens fractions. The peptide interacts with [alpha]B-crystallin at multiple sites, suppresses [alpha]-crystallin chaperone activity, increases the surface hydrophobicity, decreases the solubility and induces its aggregation. A sequential proline scan studies shows those residues 71-77 critical for the activity of the peptide. Lens extracts exhibit protease activity that generates [alpha]A66-80. Thus, the [alpha]-crystallin-derived peptide could play a role in the pathogenesis of cataract formation.
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