7n37 | pdb_00007n37
Crystal structure of 3-site deamidated variant of human gamma(S)-crystallin
Structural highlights
DiseaseCRYGS_HUMAN Early-onset lamellar cataract;Early-onset sutural cataract. The disease is caused by mutations affecting the gene represented in this entry. FunctionCRYGS_HUMAN Crystallins are the dominant structural components of the vertebrate eye lens. Publication Abstract from PubMedCataract, a clouding of the eye lens from protein precipitation, affects millions of people every year. The lens proteins, the crystallins, show extensive post-translational modifications (PTMs) in cataractous lenses. The most common PTMs, deamidation and oxidation, promote crystallin aggregation; however, it is not clear precisely how these PTMs contribute to crystallin insolubilization. Here, we report six crystal structures of the lens protein gammaS-crystallin (gammaS): one of the wild-type and five of deamidated gammaS variants, from three to nine deamidation sites, after sample aging. The deamidation mutations do not change the overall fold of gammaS; however, increasing deamidation leads to accelerated disulfide-bond formation. Addition of deamidated sites progressively destabilized protein structure, and the deamidated variants display an increased propensity for aggregation. These results suggest that the deamidated variants are useful as models for accelerated aging; the structural changes observed provide support for redox activity of gammaS-crystallin in the lens. Deamidation of the human eye lens protein gammaS-crystallin accelerates oxidative aging.,Norton-Baker B, Mehrabi P, Kwok AO, Roskamp KW, Rocha MA, Sprague-Piercy MA, von Stetten D, Miller RJD, Martin RW Structure. 2022 May 5;30(5):763-776.e4. doi: 10.1016/j.str.2022.03.002. Epub 2022, Mar 25. PMID:35338852[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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