Insight into Pathogenic Mechanism Underlying the Hereditary Cataract Caused by βB2-G149V Mutation

Wu, Jing; Chen, Silong; Xu, Jingjie; Xu, Wanyue; Zheng, Sifan; Tian, Qing; Luo, Chenqi; Chen, Xiangjun; Shentu, Xingchao

doi:10.3390/biom13050864

Open AccessArticle

Insight into Pathogenic Mechanism Underlying the Hereditary Cataract Caused by βB2-G149V Mutation

by

Jing Wu

^1,2,†,

Silong Chen

^1,†,

Jingjie Xu

^1,†,

Wanyue Xu

³,

Sifan Zheng

⁴,

Qing Tian

³,

Chenqi Luo

¹,

Xiangjun Chen

^1,3,*

and

Xingchao Shentu

^1,*

¹

Department of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310030, China

²

Department of Ophthalmology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, 158 Shangtang Road, Hangzhou 310053, China

³

Institute of Translational Medicine, Zhejiang University School of Medicine, 268 Kaixuan Road, Hangzhou 310030, China

⁴

GKT School of Medical Education, King’s College London, London SE1 1UL, UK

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Biomolecules 2023, 13(5), 864; https://doi.org/10.3390/biom13050864

Submission received: 16 November 2022 / Revised: 17 April 2023 / Accepted: 15 May 2023 / Published: 19 May 2023

(This article belongs to the Section Biomacromolecules: Proteins, Nucleic Acids and Carbohydrates)

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Abstract

Congenital cataracts account for approximately 5–20% of childhood blindness worldwide and 22–30% of childhood blindness in developing countries. Genetic disorders are the primary cause of congenital cataracts. In this work, we investigated the underlying molecular mechanism of G149V point missense mutation in βB2-crystallin, which was first identified in a three-generation Chinese family with two affected members diagnosed with congenital cataracts. Spectroscopic experiments were performed to determine the structural differences between the wild type (WT) and the G149V mutant of βB2-crystallin. The results showed that the G149V mutation significantly changed the secondary and tertiary structure of βB2-crystallin. The polarity of the tryptophan microenvironment and the hydrophobicity of the mutant protein increased. The G149V mutation made the protein structure loose and the interaction between oligomers was reduced, which decreased the stability of the protein. Furthermore, we compared βB2-crystallin WT and the G149V mutant with their biophysical properties under environmental stress. We found that the G149V mutation makes βB2-crystallin more sensitive to environmental stresses (oxidative stress, UV irradiation, and heat shock) and more likely to aggregate and form precipitation. These features might be important to the pathogenesis of βB2-crystallin G149V mutant related to congenital cataracts.

Keywords: congenital cataract; βB2-crystallin; G149V mutation; spectral experiments

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MDPI and ACS Style

Wu, J.; Chen, S.; Xu, J.; Xu, W.; Zheng, S.; Tian, Q.; Luo, C.; Chen, X.; Shentu, X. Insight into Pathogenic Mechanism Underlying the Hereditary Cataract Caused by βB2-G149V Mutation. Biomolecules 2023, 13, 864. https://doi.org/10.3390/biom13050864

AMA Style

Wu J, Chen S, Xu J, Xu W, Zheng S, Tian Q, Luo C, Chen X, Shentu X. Insight into Pathogenic Mechanism Underlying the Hereditary Cataract Caused by βB2-G149V Mutation. Biomolecules. 2023; 13(5):864. https://doi.org/10.3390/biom13050864

Chicago/Turabian Style

Wu, Jing, Silong Chen, Jingjie Xu, Wanyue Xu, Sifan Zheng, Qing Tian, Chenqi Luo, Xiangjun Chen, and Xingchao Shentu. 2023. "Insight into Pathogenic Mechanism Underlying the Hereditary Cataract Caused by βB2-G149V Mutation" Biomolecules 13, no. 5: 864. https://doi.org/10.3390/biom13050864

APA Style

Wu, J., Chen, S., Xu, J., Xu, W., Zheng, S., Tian, Q., Luo, C., Chen, X., & Shentu, X. (2023). Insight into Pathogenic Mechanism Underlying the Hereditary Cataract Caused by βB2-G149V Mutation. Biomolecules, 13(5), 864. https://doi.org/10.3390/biom13050864

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Insight into Pathogenic Mechanism Underlying the Hereditary Cataract Caused by βB2-G149V Mutation

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