Work

Disulfide cross‐links in the interaction of a cataract‐linked αA‐crystallin mutant with βB1‐crystallin

Year: 2008

Type: article

Abstract: 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.

Source: FEBS Letters

DOI: 10.1016/j.febslet.2008.11.047

Authors: M. Satish Kumar, Hanane A. Koteiche, Derek P. Claxton, Hassane S. Mchaourab

Institution: Vanderbilt University

Language: English

Topic: Heat shock proteins research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, U.S. Public Health Service, National Eye Institute