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Article

Structure of Nanobody Nb23

1
Science Division, New York University Abu Dhabi, Abu Dhabi 129188, United Arab Emirates
2
Department of Chemistry and Magnetic Resonance Center, University of Florence, 50019 Florence, Italy
3
Structural Biology Brussels, Vrije Universiteit Brussel, B-1050 Brussels, Belgium
4
VIB-VUB Center for Structural Biology, Vlaams Instituut voor Biotechnologie, B-1050 Brussels, Belgium
5
Dipartimento di Scienze Matematiche, Informatiche, e Fisiche, Udine University, 33100 Udine, Italy
6
Istituto Nazionale Biostrutture e Biosistemi, 00136 Roma, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Marilisa Leone
Molecules 2021, 26(12), 3567; https://doi.org/10.3390/molecules26123567
Received: 13 April 2021 / Revised: 10 May 2021 / Accepted: 21 May 2021 / Published: 11 June 2021
Background: Nanobodies, or VHHs, are derived from heavy chain-only antibodies (hcAbs) found in camelids. They overcome some of the inherent limitations of monoclonal antibodies (mAbs) and derivatives thereof, due to their smaller molecular size and higher stability, and thus present an alternative to mAbs for therapeutic use. Two nanobodies, Nb23 and Nb24, have been shown to similarly inhibit the self-aggregation of very amyloidogenic variants of β2-microglobulin. Here, the structure of Nb23 was modeled with the Chemical-Shift (CS)-Rosetta server using chemical shift assignments from nuclear magnetic resonance (NMR) spectroscopy experiments, and used as prior knowledge in PONDEROSA restrained modeling based on experimentally assessed internuclear distances. Further validation was comparatively obtained with the results of molecular dynamics trajectories calculated from the resulting best energy-minimized Nb23 conformers. Methods: 2D and 3D NMR spectroscopy experiments were carried out to determine the assignment of the backbone and side chain hydrogen, nitrogen and carbon resonances to extract chemical shifts and interproton separations for restrained modeling. Results: The solution structure of isolated Nb23 nanobody was determined. Conclusions: The structural analysis indicated that isolated Nb23 has a dynamic CDR3 loop distributed over different orientations with respect to Nb24, which could determine differences in target antigen affinity or complex lability. View Full-Text
Keywords: nanobody; protein structure; immunoglobulin domain; NMR nanobody; protein structure; immunoglobulin domain; NMR
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MDPI and ACS Style

Percipalle, M.; Hunashal, Y.; Steyaert, J.; Fogolari, F.; Esposito, G. Structure of Nanobody Nb23. Molecules 2021, 26, 3567. https://doi.org/10.3390/molecules26123567

AMA Style

Percipalle M, Hunashal Y, Steyaert J, Fogolari F, Esposito G. Structure of Nanobody Nb23. Molecules. 2021; 26(12):3567. https://doi.org/10.3390/molecules26123567

Chicago/Turabian Style

Percipalle, Mathias; Hunashal, Yamanappa; Steyaert, Jan; Fogolari, Federico; Esposito, Gennaro. 2021. "Structure of Nanobody Nb23" Molecules 26, no. 12: 3567. https://doi.org/10.3390/molecules26123567

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