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Kim, Ho Min
단백질 커뮤니케이션 그룹
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Structure-based glycoengineering of interferon lambda 4 enhances its productivity and anti-viral potency

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Title
Structure-based glycoengineering of interferon lambda 4 enhances its productivity and anti-viral potency
Author(s)
Chung J.-H.; Hong S.-H.; Seo N.; Kim T.-S.; An H.J.; Lee P.; Eui Cheol, Shin; Ho Min Kim
Publication Date
2020-01
Journal
CYTOKINE, v.125, pp.154833
Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Abstract
© 2019 Elsevier LtdInterferon lambda 4 (IFNλ4) has been recently known and studied for its role in hepatitis C virus (HCV) infection, but its clinical potential is significantly hampered due to its poor expression in vitro. Our study reports the successful production of IFNλ4 from a mammalian cell line through a glycoengineering and structure-based approach. We introduced de novo N-glycosylation of IFNλ4, guided by structural analysis, and produced IFNλ4 variants in Expi293F that displayed improved expression and potency. To preserve the structure and functionality of IFNλ4, the model structure of the IFNλ4 signaling complex was analyzed and the N-glycosylation candidate sites were selected. The receptor binding activity of engineered IFNλ4 variants and their receptor-mediated signaling pathway were similar to the E. coli version of IFNλ4 (eIFNλ4), while the antiviral activity and induction levels of interferon-stimulated gene (ISG) were all more robust in our variants. Our engineered IFNλ4 variants may be further developed for clinical applications and utilized in basic research to decipher the immunological roles of IFNλ4
URI
https://pr.ibs.re.kr/handle/8788114/6255
DOI
10.1016/j.cyto.2019.154833
ISSN
1043-4666
Appears in Collections:
Pioneer Research Center for Biomolecular and Cellular Structure(바이오분자 및 세포구조 연구단) > Protein Communication Group(단백질 커뮤니케이션 그룹) > 1. Journal Papers (저널논문)
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