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Cataract-Associated New Mutants S175G/H181Q of beta Beta 2-Crystallin and P24S/S31G of gamma D-Crystallin Are Involved in Protein Aggregation by Structural Changes

Title
Cataract-Associated New Mutants S175G/H181Q of beta Beta 2-Crystallin and P24S/S31G of gamma D-Crystallin Are Involved in Protein Aggregation by Structural Changes
Authors
Song, In-KangNa, SeungjinPaek, EunokLee, Kong-Joo
Ewha Authors
이공주
SCOPUS Author ID
이공주scopus
Issue Date
2020
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
1422-0067JCR Link
Citation
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol. 21, no. 18
Keywords
beta Beta 2-crystallingamma D-crystallincataract-associated mutantsproteomics datasethydrogen-deuterium exchange-MSstructural changestability changepost translational modificationprotein aggregation
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
beta/gamma-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 beta/gamma-crystallins in lens proteomic dataset of cataract patients using bioinformatics tools. Of these, two double mutants, S175G/H181Q of beta Beta 2-crystallin and P24S/S31G of gamma D-crystallin, were found mutations occurred in the largest loop linking the distant beta-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 beta/gamma-crystallin, possibly causing cataracts. This finding suggests that both the double mutants can serve as biomarkers of cataracts.
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DOI
10.3390/ijms21186504
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약학대학 > 약학과 > Journal papers
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