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


Kumar MSM Satish , Koteiche HA Hanane A , Claxton DP Derek P , Mchaourab HS Hassane S . FEBS letters. 2009 1 5; 583(1). 175-9


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.