KMID : 1094720210260060985
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Biotechnology and Bioprocess Engineering 2021 Volume.26 No. 6 p.985 ~ p.992
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Structural Study on the Impact of S239D/I332E Mutations in the Binding of Fc and Fc¥ãRIIIa
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Jebamani Petrina
Sriramulu Dinesh Kumar Jung Sang-Taek Lee Sun-Gu
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Abstract
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Engineering of Fc for improved affinity to its receptor, Fc¥ãRIIIa, can enhance the therapeutic activity of monoclonal antibodies. S239D/I332E mutation of Fc has been extensively employed in various Fc engineering studies. Still, it is not clear how the mutations have structurally influenced the molecular interactions between Fc and Fc¥ãRIIIa. In this study, the point or combined mutations of S239D/I332E were introduced into one chain (A) or the other chain (chain B) of the homodimeric Fc domain computationally. Their structural effects on the binding to Fc¥ãRIIIa were investigated through a computational docking method. These results showed that the chain-specific point mutation, S239D induced a new salt-bridge with the receptor in A and B chains of Fc, whereas I332E mutation generated a new salt-bridge with the receptor only in A chain. The combined mutation study identified that the Fc variant with four mutations reproduced the three salt-bridges. This showed that the mutation of S239D and I332E in chain A of Fc induced complex salt-bridge formation with the Lys158 of Fc¥ãRIIIa. This study is expected to provide more structural insight into Fc variants¡¯ design based on S239D/I332E mutation.
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KEYWORD
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Fc, Fc¥ãRIIIa, in silico mutation, protein-protein docking, salt-bridges
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