title: αA-crystallin peptide SDRDKFVIFLDVKHF accumulating in aging lens impairs the function of α-crystallin and induces lens protein aggregation.
abstract: BACKGROUND
  The eye lens is composed of fiber cells that are filled with α-, β- and γ-crystallins. The primary function of crystallins is to maintain the clarity of the lens through ordered interactions as well as through the chaperone-like function of α-crystallin. With aging, the chaperone function of α-crystallin decreases, with the concomitant accumulation of water-insoluble, light-scattering oligomers and crystallin-derived peptides. The role of crystallin-derived peptides in age-related lens protein aggregation and insolubilization is not understood.
  
  
  RESULTS
  We found that αA-crystallin-derived peptide, (66)SDRDKFVIFLDVKHF(80), which accumulates in the aging lens, can inhibit the chaperone activity of α-crystallin and cause aggregation and precipitation of lens crystallins. Age-related change in the concentration of αA-(66-80) peptide was estimated by mass spectrometry. The interaction of the peptide with native crystallin was studied by multi-angle light scattering and fluorescence methods. High molar ratios of peptide-to-crystallin were favourable for aggregation and precipitation. Time-lapse recordings showed that, in the presence of αA-(66-80) peptide, α-crystallin aggregates and functions as a nucleus for protein aggregation, attracting aggregation of additional α-, β- and γ-crystallins. Additionally, the αA-(66-80) peptide shares the principal properties of amyloid peptides, such as β-sheet structure and fibril formation.
  
  
  CONCLUSIONS
  These results suggest that crystallin-derived peptides such as αA-(66-80), generated in vivo, can induce age-related lens changes by disrupting the structure and organization of crystallins, leading to their insolubilization. The accumulation of such peptides in aging lenses may explain a novel mechanism for age-related crystallin aggregation and cataractogenesis.
authors.affiliation: Department of Ophthalmology, University of Missouri-Columbia School of Medicine, Columbia, Missouri, United States of America.
authors.forename: Puttur
authors.initials: P
authors.lastname: Santhoshkumar
authors.forename: Murugesan
authors.initials: M
authors.lastname: Raju
authors.forename: K Krishna
authors.initials: KK
authors.lastname: Sharma
mesh_terms: D000375:Aging / Q000378:metabolism*; D000595:Amino Acid Sequence; D002386:Cataract / Q000378:metabolism; D011232:Chemical Precipitation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007908:Lens, Crystalline / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012995:Solubility; D038202:alpha-Crystallin A Chain / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D038202:alpha-Crystallin A Chain