دورية أكاديمية

Insights into the dual nature of αB-crystallin chaperone activity from the p.P39L mutant at the N-terminal region

التفاصيل البيبلوغرافية
العنوان: Insights into the dual nature of αB-crystallin chaperone activity from the p.P39L mutant at the N-terminal region
المؤلفون: Anis Barati, Leila Rezaei Somee, Mohammad Bagher Shahsavani, Atiyeh Ghasemi, Masaru Hoshino, Jun Hong, Ali Akbar Saboury, Ali Akbar Moosavi-Movahedi, Giulio Agnetti, Reza Yousefi
المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-15 (2024)
بيانات النشر: Nature Portfolio, 2024.
سنة النشر: 2024
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Abstract The substitution of leucine to proline at position 39 (p.P39L) in human αB-crystallin (αB-Cry) has been associated with conflicting interpretations of pathogenicity in cataracts and cardiomyopathy. This study aimed to investigate the effects of the p.P39L mutation on the structural and functional features of human αB-Cry. The mutant protein was expressed in Escherichia coli (E. coli) and purified using anion exchange chromatography. We employed a wide range of spectroscopic analyses, gel electrophoresis, transmission electron microscopy (TEM), and atomic force microscopy (AFM) techniques to investigate the structure, function, stability, and fibrillation propensity of the mutant protein. The p.P39L mutation caused significant changes in the secondary, tertiary, and quaternary structures of human αB-Cry and increased the thermal stability of the protein. The mutant αB-Cry exhibited an increased chaperone activity and an altered oligomeric size distribution, along with an increased propensity to form amyloid aggregates. It is worth mentioning, increased chaperone activity has important positive and negative effects on damaged cells related to cataracts and cardiomyopathy, particularly by interfering in the process of apoptosis. Despite the apparent positive nature of the increased chaperone activity, it is also linked to adverse consequences. This study provides important insights into the effect of proline substitution by leucine at the N-terminal region on the dual nature of chaperone activity in human αB-Cry, which can act as a double-edged sword.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-024-57651-5
URL الوصول: https://doaj.org/article/872c6124bb044f8cb49a8c3a62b11322
رقم الأكسشن: edsdoj.872c6124bb044f8cb49a8c3a62b11322
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-024-57651-5