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Structural and functional studies of D109A human $\upalpha$B-crystallin contributing to the development of cataract and cardiomyopathy diseasesстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 4 марта 2022 г.
- Авторы: Hafizi Mahtab, Chebotareva Natalia A., Ghahramani Maryam, Moosavi-Movahedi Faezeh, Khaleghinejad Seyed Hossein, Kurganov Boris I., Moosavi-Movahedi Ali Akbar, Yousefi Reza
- Журнал: PLoS ONE
- Том: 16
- Номер: 11
- Год издания: 2021
- Издательство: Public Library of Science
- Местоположение издательства: United States
- Первая страница: e0260306
- DOI: 10.1371/journal.pone.0260306
- Аннотация: Alpha-B-crystallin (heat shock protein β5/HSPB5) is a member of the family of small heat shock proteins that is expressed in various organs of the human body including eye lenses and muscles. Therefore, mutations in the gene of this protein (CRYAB) might have many pathological consequences. A new mutation has recently been discovered in the alpha-crystallin domain of this chaperone protein which replaces aspartate 109 with alanine (D109A). This mutation can cause myofibrillar myopathy (MFM), cataracts, and cardiomyopathy. In the current study, several spectroscopic and microscopic analyses, as well as gel electrophoresis assessment were applied to elucidate the pathogenic contribution of human B-crystallin bearing D109A mutation in development of eye lens cataract and myopathies. The protein oligomerization, chaperone-like activity and chemical/thermal stabilities of the mutant and wild-type protein were also investigated in the comparative assessments. Our results suggested that the D109A mutation has a significant impact on the important features of human Bcrystallin, including its structure, size of the protein oligomers, tendency to form amyloid fibrils, stability, and chaperone-like activity. Given the importance of aspartate 109 in maintaining the proper structure of the -crystallin domain, its role in the dimerization and chaperone-like activity, as well as preserving protein stability through the formation of salt bridges; mutation at this important site might have critical consequences and can explain the genesis of myopathy and cataract disorders. Also, the formation of large light-scattering aggregates and disruption of the chaperone-like activity by D109A mutation might be considered as important contributing factors in development of the eye lens opacity.
- Добавил в систему: Чеботарева Наталья Александровна