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    FEBS Lett. 2009 Jan 5;583(1):175-9. Epub 2008 Dec 9.

    Disulfide cross-links in the interaction of a cataract-linked alphaA-crystallin mutant with betaB1-crystallin.

    Kumar MS, Koteiche HA, Claxton DP, Mchaourab HS.

    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.

    A number of alphaA-crystallin mutants are associated with hereditary cataract including cysteine substitution at arginine 49. We report the formation of affinity-driven disulfide bonds in the interaction of alphaA-R49C with betaB1-crystallin. To mimic cysteine thiolation in the lens, betaB1-crystallin was modified by a bimane probe through a disulfide linkage. Our data suggest a mechanism whereby a transient disulfide bond occurs between alphaA- and betaB1-crystallin followed by a disulfide exchange with cysteine 49 of a neighboring alphaA-crystallin subunit. This is the first investigation of disulfide bonds in the confine of the chaperone/substrate complex where reaction rates are favored by orders of magnitude. Covalent protein cross-links are a hallmark of age-related cataract and may be a factor in its inherited form.

    PMID: 19071118 [PubMed - indexed for MEDLINE]

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