Dataset Information

?A-crystallin peptide SDRDKFVIFLDVKHF accumulating in aging lens impairs the function of ?-crystallin and induces lens protein aggregation.

ABSTRACT:

Background

The eye lens is composed of fiber cells that are filled with ?-, ?- and ?-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 ?-crystallin. With aging, the chaperone function of ?-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.

Methodology/principal findings

We found that ?A-crystallin-derived peptide, (66)SDRDKFVIFLDVKHF(80), which accumulates in the aging lens, can inhibit the chaperone activity of ?-crystallin and cause aggregation and precipitation of lens crystallins. Age-related change in the concentration of ?A-(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 ?A-(66-80) peptide, ?-crystallin aggregates and functions as a nucleus for protein aggregation, attracting aggregation of additional ?-, ?- and ?-crystallins. Additionally, the ?A-(66-80) peptide shares the principal properties of amyloid peptides, such as ?-sheet structure and fibril formation.

Conclusions/significance

These results suggest that crystallin-derived peptides such as ?A-(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.

SUBMITTER: Santhoshkumar P

PROVIDER: S-EPMC3084282 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Publications

αA-crystallin peptide SDRDKFVIFLDVKHF accumulating in aging lens impairs the function of α-crystallin and induces lens protein aggregation.

Santhoshkumar Puttur P Raju Murugesan M Sharma K Krishna KK

PloS one 20110428 4

<h4>Background</h4>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-rel ...[more]

PMID: 21552534

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