H101G Mutation in Rat Lens αB-Crystallin Alters Chaperone Activity and
Divalent Metal Ion Binding
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Published:2022-04
Issue:5
Volume:23
Page:719-727
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ISSN:1389-2010
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Container-title:Current Pharmaceutical Biotechnology
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language:en
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Short-container-title:CPB
Author:
Wu Yi-Ying1ORCID,
Desu Naveen Kumar Reddy1ORCID,
Lu Shou-Yun1ORCID,
Yu Bi-Yu1ORCID,
Kumar Ramya2ORCID,
Huang Fu-Yung1ORCID
Affiliation:
1. Department of Chemistry, National Cheng Kung University, Tainan, Taiwan
2. Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan,Taiwan
Abstract
Background:
The molecular chaperone function of αB-crystallins is heavily involved in maintaining lens transparency and the development of cataracts.
Objective:
The aim of the study was to investigate whether divalent metal ion binding improves the stability and αB-crystallin chaperone activity.
Methods:
In this study, we have developed an H101G αB-crystallin mutant and compared the surface hydrophobicity, chaperone activity, and secondary and tertiary structure with the wild type in the presence and absence of metal ions.
Results:
Substitution of His101 with glycine resulted in structural and functional changes. Spectral analysis and chaperone-like activity assays showed that substitution of glycine resulted in a higher percentage of random coils, increased hydrophobicity, and 22±2% higher chaperone-like activity. Whereas in the presence of the Cu2+ ion, H101G exhibited 32±1% less chaperone-like activity compared to the wild type.
Conclusion:
Cu2+ has been reported to enhance the chaperone-like activity of lens α-crystallin. Our results indicate that H101 is the predominant Cu2+ binding site, and the mutation resulted in a partial unfolding that impaired the binding of Cu2+ to H101 residue. In conclusion, this study further helps to understand the important binding site for Cu2+ to αB-crystallin.
Funder
Department of Chemistry National Cheng Kung University, Tainan
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmaceutical Science,Biotechnology