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Quantification of Multivalent Interactions between Sialic Acid and Influenza A Virus Spike Proteins by Single-Molecule Force Spectroscopy

Jose Luis Cuellar-Camacho Orcid Logo, Sumati Bhatia Orcid Logo, Valentin Reiter-Scherer, Daniel Lauster, Susanne Liese Orcid Logo, Jürgen P. Rabe Orcid Logo, Andreas Herrmann Orcid Logo, Rainer Haag Orcid Logo

Journal of the American Chemical Society, Volume: 142, Issue: 28, Pages: 12181 - 12192

Swansea University Author: Sumati Bhatia Orcid Logo

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DOI (Published version): 10.1021/jacs.0c02852

Abstract

Multivalency is a key principle in reinforcing reversible molecular interactions through the formation of multiple bonds. The influenza A virus deploys this strategy to bind strongly to cell surface receptors. We performed single-molecule force spectroscopy (SMFS) to investigate the rupture force re...

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Published in: Journal of the American Chemical Society
ISSN: 0002-7863 1520-5126
Published: American Chemical Society (ACS) 2020
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URI: https://cronfa.swan.ac.uk/Record/cronfa64865
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spelling v2 64865 2023-11-01 Quantification of Multivalent Interactions between Sialic Acid and Influenza A Virus Spike Proteins by Single-Molecule Force Spectroscopy a6b1181ebdbe42bd03b24cbdb559d082 0000-0002-5123-4937 Sumati Bhatia Sumati Bhatia true false 2023-11-01 CHEM Multivalency is a key principle in reinforcing reversible molecular interactions through the formation of multiple bonds. The influenza A virus deploys this strategy to bind strongly to cell surface receptors. We performed single-molecule force spectroscopy (SMFS) to investigate the rupture force required to break individual and multiple bonds formed between synthetic sialic acid (SA) receptors and the two principal spike proteins of the influenza A virus (H3N2): hemagglutinin (H3) and neuraminidase (N2). Kinetic parameters such as the rupture length (χβ) and dissociation rate (koff) are extracted using the model by Friddle, De Yoreo, and Noy. We found that a monovalent SA receptor binds to N2 with a significantly higher bond lifetime (270 ms) compared to that for H3 (36 ms). By extending the single-bond rupture analysis to a multibond system of n protein-receptor pairs, we provide an unprecedented quantification of the mechanistic features of multivalency between H3 and N2 with SA receptors and show that the stability of the multivalent connection increases with the number of bonds from tens to hundreds of milliseconds. Association rates (kon) are also provided, and an estimation of the dissociation constants (KD) between the SA receptors to both proteins indicate a 17-fold higher binding affinity for the SA–N2 bond with respect to that of SA–H3. An optimal designed multivalent SA receptor showed a higher binding stability to the H3 protein of the influenza A virus than to the monovalent SA receptor. Our study emphasizes the influence of the scaffold on the presentation of receptors during multivalent binding. Journal Article Journal of the American Chemical Society 142 28 12181 12192 American Chemical Society (ACS) 0002-7863 1520-5126 Force spectroscopy, Receptors, Screening assays, Stability, Viruses 15 7 2020 2020-07-15 10.1021/jacs.0c02852 http://dx.doi.org/10.1021/jacs.0c02852 COLLEGE NANME Chemistry COLLEGE CODE CHEM Swansea University 2024-01-02T10:19:41.4907577 2023-11-01T10:39:13.4207079 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry Jose Luis Cuellar-Camacho 0000-0002-9218-2678 1 Sumati Bhatia 0000-0002-5123-4937 2 Valentin Reiter-Scherer 3 Daniel Lauster 4 Susanne Liese 0000-0001-7420-5488 5 Jürgen P. Rabe 0000-0003-0847-6663 6 Andreas Herrmann 0000-0002-6716-2026 7 Rainer Haag 0000-0003-3840-162x 8
title Quantification of Multivalent Interactions between Sialic Acid and Influenza A Virus Spike Proteins by Single-Molecule Force Spectroscopy
spellingShingle Quantification of Multivalent Interactions between Sialic Acid and Influenza A Virus Spike Proteins by Single-Molecule Force Spectroscopy
Sumati Bhatia
title_short Quantification of Multivalent Interactions between Sialic Acid and Influenza A Virus Spike Proteins by Single-Molecule Force Spectroscopy
title_full Quantification of Multivalent Interactions between Sialic Acid and Influenza A Virus Spike Proteins by Single-Molecule Force Spectroscopy
title_fullStr Quantification of Multivalent Interactions between Sialic Acid and Influenza A Virus Spike Proteins by Single-Molecule Force Spectroscopy
title_full_unstemmed Quantification of Multivalent Interactions between Sialic Acid and Influenza A Virus Spike Proteins by Single-Molecule Force Spectroscopy
title_sort Quantification of Multivalent Interactions between Sialic Acid and Influenza A Virus Spike Proteins by Single-Molecule Force Spectroscopy
author_id_str_mv a6b1181ebdbe42bd03b24cbdb559d082
author_id_fullname_str_mv a6b1181ebdbe42bd03b24cbdb559d082_***_Sumati Bhatia
author Sumati Bhatia
author2 Jose Luis Cuellar-Camacho
Sumati Bhatia
Valentin Reiter-Scherer
Daniel Lauster
Susanne Liese
Jürgen P. Rabe
Andreas Herrmann
Rainer Haag
format Journal article
container_title Journal of the American Chemical Society
container_volume 142
container_issue 28
container_start_page 12181
publishDate 2020
institution Swansea University
issn 0002-7863
1520-5126
doi_str_mv 10.1021/jacs.0c02852
publisher American Chemical Society (ACS)
college_str Faculty of Science and Engineering
hierarchytype
hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Chemistry{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Chemistry
url http://dx.doi.org/10.1021/jacs.0c02852
document_store_str 0
active_str 0
description Multivalency is a key principle in reinforcing reversible molecular interactions through the formation of multiple bonds. The influenza A virus deploys this strategy to bind strongly to cell surface receptors. We performed single-molecule force spectroscopy (SMFS) to investigate the rupture force required to break individual and multiple bonds formed between synthetic sialic acid (SA) receptors and the two principal spike proteins of the influenza A virus (H3N2): hemagglutinin (H3) and neuraminidase (N2). Kinetic parameters such as the rupture length (χβ) and dissociation rate (koff) are extracted using the model by Friddle, De Yoreo, and Noy. We found that a monovalent SA receptor binds to N2 with a significantly higher bond lifetime (270 ms) compared to that for H3 (36 ms). By extending the single-bond rupture analysis to a multibond system of n protein-receptor pairs, we provide an unprecedented quantification of the mechanistic features of multivalency between H3 and N2 with SA receptors and show that the stability of the multivalent connection increases with the number of bonds from tens to hundreds of milliseconds. Association rates (kon) are also provided, and an estimation of the dissociation constants (KD) between the SA receptors to both proteins indicate a 17-fold higher binding affinity for the SA–N2 bond with respect to that of SA–H3. An optimal designed multivalent SA receptor showed a higher binding stability to the H3 protein of the influenza A virus than to the monovalent SA receptor. Our study emphasizes the influence of the scaffold on the presentation of receptors during multivalent binding.
published_date 2020-07-15T10:19:43Z
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