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A Combined NMR and SAXS Analysis of the Partially Folded Cataract-Associated V75D ?D-Crystallin.


ABSTRACT: A cataract is a pathological condition characterized by the clouding of the normally clear eye lens brought about by deposition of crystallin proteins in the lens fiber cells. These protein aggregates reduce visual acuity by scattering or blocking incoming light. Chemical damage to proteins of the crystallin family, accumulated over a lifetime, leads to age-related cataract, whereas inherited mutations are associated with congenital or early-onset cataract. The V75D mutant of ?D-crystallin is associated with congenital cataract in mice and was previously shown to un/fold via a partially folded intermediate. Here, we structurally characterized the stable equilibrium urea unfolding intermediate of V75D at the ensemble level using solution NMR and small-angle x-ray scattering. Our data show that, in the intermediate, the C-terminal domain retains a folded conformation that is similar to the native wild-type protein, whereas the N-terminal domain is unfolded and comprises an ensemble of random conformers, without any detectable residual structural propensities.

SUBMITTER: Whitley MJ 

PROVIDER: S-EPMC5376099 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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A Combined NMR and SAXS Analysis of the Partially Folded Cataract-Associated V75D γD-Crystallin.

Whitley Matthew J MJ   Xi Zhaoyong Z   Bartko Jonathan C JC   Jensen Malene Ringkjøbing MR   Blackledge Martin M   Gronenborn Angela M AM  

Biophysical journal 20170301 6


A cataract is a pathological condition characterized by the clouding of the normally clear eye lens brought about by deposition of crystallin proteins in the lens fiber cells. These protein aggregates reduce visual acuity by scattering or blocking incoming light. Chemical damage to proteins of the crystallin family, accumulated over a lifetime, leads to age-related cataract, whereas inherited mutations are associated with congenital or early-onset cataract. The V75D mutant of γD-crystallin is as  ...[more]

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