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- Title
Cataract-Associated New Mutants S175G/H181Q of βΒ2-Crystallin and P24S/S31G of γD-Crystallin Are Involved in Protein Aggregation by Structural Changes.
- Authors
Song, In-Kang; Na, Seungjin; Paek, Eunok; Lee, Kong-Joo
- Abstract
β/γ-Crystallins, the main structural protein in human lenses, have highly stable structure for keeping the lens transparent. Their mutations have been linked to cataracts. In this study, we identified 10 new mutations of β/γ-crystallins in lens proteomic dataset of cataract patients using bioinformatics tools. Of these, two double mutants, S175G/H181Q of βΒ2-crystallin and P24S/S31G of γD-crystallin, were found mutations occurred in the largest loop linking the distant β-sheets in the Greek key motif. We selected these double mutants for identifying the properties of these mutations, employing biochemical assay, the identification of protein modifications with nanoUPLC-ESI-TOF tandem MS and examining their structural dynamics with hydrogen/deuterium exchange-mass spectrometry (HDX-MS). We found that both double mutations decrease protein stability and induce the aggregation of β/γ-crystallin, possibly causing cataracts. This finding suggests that both the double mutants can serve as biomarkers of cataracts.
- Subjects
CYTOSKELETAL proteins; PROTEOMICS; TANDEM mass spectrometry; STRUCTURAL dynamics; CATARACT; DEUTERIUM; PROTEIN stability
- Publication
International Journal of Molecular Sciences, 2020, Vol 21, Issue 18, p6504
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms21186504