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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

In-depth analysis of subclass-specific conformational preferences of IgG antibodies. / Tian, Xinsheng; Vestergaard, Bente; Thorolfsson, Matthias; Yang, Zhiru; Rasmussen, Hanne B.; Langkilde, Annette Eva.

In: IUCrJ, Vol. 2, No. 1, 01.01.2015, p. 9-18.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Tian, X, Vestergaard, B, Thorolfsson, M, Yang, Z, Rasmussen, HB & Langkilde, AE 2015, 'In-depth analysis of subclass-specific conformational preferences of IgG antibodies', IUCrJ, vol. 2, no. 1, pp. 9-18. https://doi.org/10.1107/S205225251402209X

APA

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, 2(1), 9-18. https://doi.org/10.1107/S205225251402209X

Vancouver

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 1;2(1):9-18. https://doi.org/10.1107/S205225251402209X

Author

Tian, Xinsheng ; Vestergaard, Bente ; Thorolfsson, Matthias ; Yang, Zhiru ; Rasmussen, Hanne B. ; Langkilde, Annette Eva. / In-depth analysis of subclass-specific conformational preferences of IgG antibodies. In: IUCrJ. 2015 ; Vol. 2, No. 1. pp. 9-18.

Bibtex

@article{68d7f3cd33824b858ad9bf2be865410a,
title = "In-depth analysis of subclass-specific conformational preferences of IgG antibodies",
abstract = "IgG subclass-specific differences in biological function and in vitro stability areoften referred to variations in the conformational flexibility, while this flexibilityhas rarely been characterized. Here, small-angle X-ray scattering data fromIgG1, IgG2 and IgG4 antibodies, which were designed with identical variableregions, were thoroughly analysed by the ensemble optimization method. Theextended analysis of the optimized ensembles through shape clustering revealsdistinct subclass-specific conformational preferences, which provide new insightsfor understanding the variations in physical/chemical stability and biologicalfunction of therapeutic antibodies. Importantly, the way that specific differencesin the linker region correlate with the solution structure of intact antibodies isrevealed, thereby visualizing future potential for the rational design ofantibodies with designated physicochemical properties and tailored effectorfunctions. In addition, this advanced computational approach is applicable toother flexible multi-domain systems and extends the potential for investigatingflexibility in solutions of macromolecules by small-angle X-ray scattering.",
author = "Xinsheng Tian and Bente Vestergaard and Matthias Thorolfsson and Zhiru Yang and Rasmussen, {Hanne B.} and Langkilde, {Annette Eva}",
year = "2015",
month = jan,
day = "1",
doi = "10.1107/S205225251402209X",
language = "English",
volume = "2",
pages = "9--18",
journal = "I U Cr J",
issn = "2052-2525",
publisher = "International Union of Crystallography",
number = "1",

}

RIS

TY - JOUR

T1 - In-depth analysis of subclass-specific conformational preferences of IgG antibodies

AU - Tian, Xinsheng

AU - Vestergaard, Bente

AU - Thorolfsson, Matthias

AU - Yang, Zhiru

AU - Rasmussen, Hanne B.

AU - Langkilde, Annette Eva

PY - 2015/1/1

Y1 - 2015/1/1

N2 - IgG subclass-specific differences in biological function and in vitro stability areoften referred to variations in the conformational flexibility, while this flexibilityhas rarely been characterized. Here, small-angle X-ray scattering data fromIgG1, IgG2 and IgG4 antibodies, which were designed with identical variableregions, were thoroughly analysed by the ensemble optimization method. Theextended analysis of the optimized ensembles through shape clustering revealsdistinct subclass-specific conformational preferences, which provide new insightsfor understanding the variations in physical/chemical stability and biologicalfunction of therapeutic antibodies. Importantly, the way that specific differencesin the linker region correlate with the solution structure of intact antibodies isrevealed, thereby visualizing future potential for the rational design ofantibodies with designated physicochemical properties and tailored effectorfunctions. In addition, this advanced computational approach is applicable toother flexible multi-domain systems and extends the potential for investigatingflexibility in solutions of macromolecules by small-angle X-ray scattering.

AB - IgG subclass-specific differences in biological function and in vitro stability areoften referred to variations in the conformational flexibility, while this flexibilityhas rarely been characterized. Here, small-angle X-ray scattering data fromIgG1, IgG2 and IgG4 antibodies, which were designed with identical variableregions, were thoroughly analysed by the ensemble optimization method. Theextended analysis of the optimized ensembles through shape clustering revealsdistinct subclass-specific conformational preferences, which provide new insightsfor understanding the variations in physical/chemical stability and biologicalfunction of therapeutic antibodies. Importantly, the way that specific differencesin the linker region correlate with the solution structure of intact antibodies isrevealed, thereby visualizing future potential for the rational design ofantibodies with designated physicochemical properties and tailored effectorfunctions. In addition, this advanced computational approach is applicable toother flexible multi-domain systems and extends the potential for investigatingflexibility in solutions of macromolecules by small-angle X-ray scattering.

U2 - 10.1107/S205225251402209X

DO - 10.1107/S205225251402209X

M3 - Journal article

C2 - 25610623

VL - 2

SP - 9

EP - 18

JO - I U Cr J

JF - I U Cr J

SN - 2052-2525

IS - 1

ER -

ID: 129662673