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Tian X, Vestergaard B, Thorolfsson M, et al. In-depth analysis of subclass-specific conformational preferences of IgG antibodies. IUCrJ. 2015;2:9-18doi: 10.1107/S205225251402209X.
Tian, X., Vestergaard, B., Thorolfsson, M., Yang, Z., Rasmussen, H. B., & Langkilde, A. E. (2015). In-depth analysis of subclass-specific conformational preferences of IgG antibodies. IUCrJ, 29-18. https://doi.org/10.1107/S205225251402209X
Tian, Xinsheng, et al. "In-depth analysis of subclass-specific conformational preferences of IgG antibodies." IUCrJ vol. 2 (2015): 9-18. doi: https://doi.org/10.1107/S205225251402209X
Tian X, Vestergaard B, Thorolfsson M, Yang Z, Rasmussen HB, Langkilde AE. In-depth analysis of subclass-specific conformational preferences of IgG antibodies. IUCrJ. 2015 Jan 01;2:9-18. doi: 10.1107/S205225251402209X. eCollection 2015 Jan 01. PMID: 25610623; PMCID: PMC4285876.
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IUCrJ. 2015 Jan 01;2:9-18. doi: 10.1107/S205225251402209X. eCollection 2015 Jan 01.

In-depth analysis of subclass-specific conformational preferences of IgG antibodies.

IUCrJ

Xinsheng Tian, Bente Vestergaard, Matthias Thorolfsson, Zhiru Yang, Hanne B Rasmussen, Annette E Langkilde

Affiliations

  1. Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark.
  2. Biopharmaceuticals Research Unit, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Måløv, Denmark.
  3. Biopharmaceuticals Research Unit, Novo Nordisk A/S, Life Science Park Road 29, Beijing 102206, People's Republic of China.

PMID: 25610623 PMCID: PMC4285876 DOI: 10.1107/S205225251402209X

Abstract

IgG subclass-specific differences in biological function and in vitro stability are often referred to variations in the conformational flexibility, while this flexibility has rarely been characterized. Here, small-angle X-ray scattering data from IgG1, IgG2 and IgG4 antibodies, which were designed with identical variable regions, were thoroughly analysed by the ensemble optimization method. The extended analysis of the optimized ensembles through shape clustering reveals distinct subclass-specific conformational preferences, which provide new insights for understanding the variations in physical/chemical stability and biological function of therapeutic antibodies. Importantly, the way that specific differences in the linker region correlate with the solution structure of intact antibodies is revealed, thereby visualizing future potential for the rational design of antibodies with designated physicochemical properties and tailored effector functions. In addition, this advanced computational approach is applicable to other flexible multi-domain systems and extends the potential for investigating flexibility in solutions of macromolecules by small-angle X-ray scattering.

Keywords: IgG antibody; shape clustering; small-angle X-ray scattering (SAXS); solution conformation; structure modelling

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