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Title 

Design of a binding scaffold based on variable lymphocyte receptors of jawless vertebrates by module engineering

 

모듈단백질 조합에 의한 결합스캐폴드 디자인

Authors 

S C LeeK ParkJ HanJ J LeeH J KimS HongW HeuYu Jung KimJ S HaSeung Goo LeeH K CheongY H JeonD KimH S Kim

Publisher 

National Academy of Sciences

Issue Date 

2012

Citation 

Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 9, pp. 3299-3304

Keywords 

Modular architectureMolecular binderNon-antibody scaffoldRepeat protein

Abstract 

Repeat proteins have recently been of great interest as potential alternatives to immunoglobulin antibodies due to their unique structural and biophysical features. We here present the development of a binding scaffold based on variable lymphocyte receptors, which are nonimmunoglobulin antibodies composed of Leucinerich repeat modules in jawless vertebrates, by module engineering. A template scaffold was first constructed by joining consensus repeat modules between the N- and C-capping motifs of variable lymphocyte receptors. The N-terminal domain of the template scaffold was redesigned based on the internalin-B cap by analyzing the modular similarity between the respective repeat units using a computational approach. The newly designed scaffold, termed "Repebody," showed a high level of soluble expression in bacteria, displaying high thermodynamic and pH stabilities. Ease of molecular engineering was shown by designing repebodies specific for myeloid differentiation protein-2 and hen egg lysozyme, respectively, by a rational approach. The crystal structures of designed repebodies were determined to elucidate the structural features and interaction interfaces. We demonstrate general applicability of the scaffold by selecting repebodies with different binding affinities for interleukin-6 using phage display.

ISSN 

0027-8424

Link 

http://dx.doi.org/10.1073/pnas.1113193109

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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