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Cataract-linked ?D-crystallin mutants have weak affinity to lens chaperones ?-crystallins.

ABSTRACT: To test the hypothesis that ?-crystallin chaperone activity plays a central role in maintenance of lens transparency, we investigated its interactions with ?-crystallin mutants that cause congenital cataract in mouse models. Although the two substitutions, I4F and V76D, stabilize a partially unfolded ?D-crystallin intermediate, their affinities to ?-crystallin are marginal even at relatively high concentrations. Detectable binding required further reduction of ?D-crystallin stability which was achieved by combining the two mutations. Our results demonstrate that mutants and possibly age-damaged ?-crystallin can escape quality control by lens chaperones rationalizing the observation that they nucleate protein aggregation and lead to cataract.

SUBMITTER: Mishra S 

PROVIDER: S-EPMC3282170 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Cataract-linked γD-crystallin mutants have weak affinity to lens chaperones α-crystallins.

Mishra Sanjay S   Stein Richard A RA   McHaourab Hassane S HS  

FEBS letters 20120128 4

To test the hypothesis that α-crystallin chaperone activity plays a central role in maintenance of lens transparency, we investigated its interactions with γ-crystallin mutants that cause congenital cataract in mouse models. Although the two substitutions, I4F and V76D, stabilize a partially unfolded γD-crystallin intermediate, their affinities to α-crystallin are marginal even at relatively high concentrations. Detectable binding required further reduction of γD-crystallin stability which was a  ...[more]

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