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Crystals 2019, 9(3), 177; https://doi.org/10.3390/cryst9030177

Fab Fragment of VHH-Based Antibody Netakimab: Crystal Structure and Modeling Interaction with Cytokine IL-17A

1
Institute of Protein Research RAS, Institutskaya 4, Pushchino, Moscow 142290, Russia
2
CJSC Biocad, ul.Svyazi., 34-A, p. Strelna, Saint-Petersburg, Leningrad 198515, Russia
*
Author to whom correspondence should be addressed.
Received: 1 March 2019 / Revised: 15 March 2019 / Accepted: 21 March 2019 / Published: 26 March 2019
(This article belongs to the Special Issue Protein Crystallography)
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Abstract

Interleukin 17A (IL-17A) is a proinflammatory cytokine produced by Th17 cells. Antibody BCD-085 (netakimab) against human IL-17A is one of the new inhibitors of this cytokine. In netakimab, the VH domain is replaced by the VHH domain of Lama glama possessing a long complementarity determining region (CDR-H3) in its heavy chain. Here we demonstrate the high affinity of IL-17A to the Fab fragment of netakimab and to its integral part, the VHH domain. We have determined the crystal structure of the Fab fragment of netakimab at 1.9 Å resolution. High variability in the orientation of light and heavy chains of the Fab fragment of netakimab was shown, which is determined by the peculiarity of the structural organization of the CDR-H3. As the high conformational plasticity of the molecule hampers modeling the Fab fragment of netakimab complexed to IL-17A, we have carried out modeling the complex between the antigen and the integral part of the Fab fragment, the VHH domain. We explain the high netakimab Fab fragment affinity for IL-17A by a large number of protein–protein contacts due to additional interactions between CDR-H3 and the cytokine dimer. View Full-Text
Keywords: VHH domain; Fab fragment; netakimab; crystal structure; complementarity determining regions; interleukin 17A VHH domain; Fab fragment; netakimab; crystal structure; complementarity determining regions; interleukin 17A
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Kostareva, O.; Kolyadenko, I.; Ulitin, A.; Ekimova, V.; Evdokimov, S.; Garber, M.; Tishchenko, S.; Gabdulkhakov, A. Fab Fragment of VHH-Based Antibody Netakimab: Crystal Structure and Modeling Interaction with Cytokine IL-17A. Crystals 2019, 9, 177.

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