Article
Biochemistry & Molecular Biology
Wanyue Xu, Jingjie Xu, Caiping Shi, Jing Wu, Huaxia Wang, Wei Wu, Xiangjun Chen, Lidan Hu
Summary: This study identified a novel mutation (Ile82Met) in gamma A-crystallin and investigated its potential molecular mechanism in cataract. The mutation was found to decrease protein stability and increase aggregatory potency under stressful conditions. Furthermore, chemical denaturation affected the unfolding process of gamma A-crystallin.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Shu-Shun Hsueh, S. -S. (Steven) Wang, Shu-Han Chen, Chia-Lin Wang, W. (Josephine) Wu, Ta-Hsien Lin
Summary: This study used NMR-solution HGDC structures as starting conformers for molecular dynamics simulations to investigate the unfolding process of HGDC and the early stages of cataractogenesis. The high-resolution details of the conformational dynamics provided insights into the domain swap theories proposed by past studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Malak Abu-Hussien, Guru Krishnakumar Viswanathan, Lia Borisover, Michael Mimouni, Hamutal Engel, Shiri Zayit-Soudry, Ehud Gazit, Daniel Segal
Summary: Gamma D-crystallin is essential in maintaining the transparency of the human eye lens, with its aggregation leading to cataract formation. The study found that cochineal Carmine could effectively reduce aggregation of gamma D-crystallin, showing potential for developing new therapeutics for cataract treatment.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Ningqin Lin, Ying Zhang, Xiaohui Song, Jingjie Xu, Chenqi Luo, Qing Tian, Ke Yao, Wei Wu, Xiangjun Chen, Lidan Hu
Summary: In this study, the pathogenic mechanisms of two mutations in the gamma D-crystallin were investigated, revealing structural disruption and aggregation formation. Furthermore, it was found that the aggregation of the mutants could be reversed by lanosterol, suggesting a potential therapeutic strategy.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Sha Zhu, Yibo Xi, Jingjie Xu, Lidan Hu, Chenqi Luo, Ke Yao, Xiangjun Chen
Summary: This study found that a specific mutation in S-crystallin (G18D mutation) leads to congenital hereditary cataracts and the mutation affects the stability of S-crystallin and promotes aggregation. These findings are important for understanding the pathogenesis of congenital cataracts.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Chenxi Fu, Jingjie Xu, Xiaoxia Yang, Xiangjun Chen, Ke Yao
Summary: This study investigated the thermal stability of gamma C-crystallin mutants and found that L45P and Y46D mutations impaired the stability. However, alpha A-crystallin could rescue the thermal stability of these mutants to some extent.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Spectroscopy
Shu-Shun Hsueh, Jian-Hong Lu, Josephine W. Wu, Ta-Hsien Lin, Steven S-S Wang
Summary: This study investigated the effect of ortho-vanillin on ultraviolet-C-induced aggregation of human gamma D-crystallin, demonstrating its dose-dependent suppression of protein aggregation. Structural changes in gamma D-crystallin induced by the interaction with ortho-vanillin were revealed, potentially contributing to the development of therapeutics for cataracts.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2021)
Article
Biochemistry & Molecular Biology
Chenxi Fu, Jingjie Xu, Zhekun Jia, Ke Yao, Xiangjun Chen
Summary: Congenital cataracts caused by genetic disorders are the primary cause of child blindness across the globe. This study investigated two mutations of gamma C-crystallin in Chinese families with nuclear congenital cataracts, revealing that these mutations destabilized the protein and increased aggregation propensity under environmental stress.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Jingjie Xu, Huaxia Wang, Ailing Wang, Jia Xu, Chenxi Fu, Zhekun Jia, Ke Yao, Xiangjun Chen
Summary: Congenital cataract is a major cause of blindness in children globally. A novel beta B2 mutation W151R was found to be prone to aggregation due to low solubility and poor structural stability, but the negative effect of the mutation was reversed by administration of lanosterol.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Amber D. Rolland, Takumi Takata, Micah T. Donor, Kirsten J. Lampi, James S. Prell
Summary: This study investigates the interactions and oligomerization kinetics of β-crystallin in the lens using native ion mobility-mass spectrometry, revealing compact ring-like topologies of the observed oligomers.
Article
Biochemistry & Molecular Biology
Susanne Weininger, Malte Neudorf, Stefan Groeger, Eric Plato, Robert Broneske, Kay Saalwaechter, Ulrich Weininger, Jochen Balbach
Summary: Crystallin proteins in the human eye lenses play a role in maintaining transparency, light refraction, and UV light protection. Imbalance in the interaction between alpha-, beta-, and gamma-crystallin can lead to cataracts. The research looks into the effects of UV-B radiation on gamma D-crystallin, specifically observing changes in the N-terminal domain. It is found that some photoprotective properties remain in extracts from cataract patients. Additionally, a genetic mutation in the eye lens core of infants with cataracts increases sensitivity to UV-B irradiation.
MACROMOLECULAR BIOSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Jing Wu, Wanyue Xu, Wei Wu, Jingjie Xu, Sifan Zheng, Xingchao Shentu, Xiangjun Chen
Summary: This study investigated the molecular mechanism of the R48C mutation of gamma A-crystallin in a Mexican-Mestizo descent family causing congenital cataracts. The R48C mutation did not affect the secondary and tertiary structure of the protein, but it did disrupt its oxidative stability, leading to increased aggregation and precipitation under oxidative conditions, potentially contributing to the pathogenesis of congenital cataracts related to this mutation.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biology
Eugene Serebryany, Sourav Chowdhury, Christopher N. Woods, David C. Thorn, Nicki E. Watson, Arthur A. McClelland, Rachel E. Klevit, Eugene Shakhnovich
Summary: Cataract, a protein aggregation disorder, is a common cause of vision loss worldwide. Researchers have discovered that myo-inositol, an abundant lens metabolite, can suppress the aggregation of lens crystallins, suggesting it as a potential strategy to prevent or delay age-onset cataracts.
Article
Biochemistry & Molecular Biology
Ajamaluddin Malik, Hajar Ahmed Almaharfi, Javed Masood Khan, Malik Hisamuddin, Salman Freeh Alamery, Samina Hyder Haq, Mohammad Z. Ahmed
Summary: Camel lens proteins show resistance to cataractogenesis in harsh conditions, with α-crystallin playing a key role in preventing aggregation of ζ-crystallin at high temperatures, exhibiting significant chaperone activity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Ophthalmology
Alan Shiels, J. Fielding Hejtmancik
Summary: Cataracts are caused by protein aggregation or disruption of lens microarchitecture, and genetic mutations can provide insights into lens homeostasis. Congenital cataracts involve severe damage to lens proteins, while age-related cataracts are more susceptible to environmental insults, leading to different pathologies.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)