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Force Spectroscopy Shows Dynamic Binding of Influenza Hemagglutinin and Neuraminidase to Sialic Acid

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

Biophysical Journal, Volume: 116, Issue: 6, Pages: 1037 - 1048

Swansea University Author: Sumati Bhatia Orcid Logo

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DOI (Published version): 10.1016/j.bpj.2019.01.041

Abstract

The influenza A virus infects target cells through multivalent interactions of its major spike proteins, hemagglutinin (HA) and neuraminidase (NA), with the cellular receptor sialic acid (SA). HA is known to mediate the attachment of the virion to the cell, whereas NA enables the release of newly fo...

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Published in: Biophysical Journal
ISSN: 0006-3495
Published: Elsevier BV 2019
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URI: https://cronfa.swan.ac.uk/Record/cronfa64870
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spelling v2 64870 2023-11-01 Force Spectroscopy Shows Dynamic Binding of Influenza Hemagglutinin and Neuraminidase to Sialic Acid a6b1181ebdbe42bd03b24cbdb559d082 0000-0002-5123-4937 Sumati Bhatia Sumati Bhatia true false 2023-11-01 CHEM The influenza A virus infects target cells through multivalent interactions of its major spike proteins, hemagglutinin (HA) and neuraminidase (NA), with the cellular receptor sialic acid (SA). HA is known to mediate the attachment of the virion to the cell, whereas NA enables the release of newly formed virions by cleaving SA from the cell. Because both proteins target the same receptor but have antagonistic functions, virus infection depends on a properly tuned balance of the kinetics of HA and NA activities for viral entry to and release from the host cell. Here, dynamic single-molecule force spectroscopy, based on scanning force microscopy, was employed to determine these bond-specific kinetics, characterized by the off rate koff, rupture length xβ and on rate kon, as well as the related free-energy barrier ΔG and the dissociation constant KD. Measurements were conducted using surface-immobilized HA and NA of the influenza A virus strain A/California/04/2009 and a novel, to our knowledge, synthetic SA-displaying receptor for functionalization of the force probe. Single-molecule force spectroscopy at force loading rates between 100 and 50,000 pN/s revealed most probable rupture forces of the protein-SA bond in the range of 10–100 pN. Using an extension of the widely applied Bell-Evans formalism by Friddle, De Yoreo, and co-workers, it is shown that HA features a smaller xβ, a larger koff and a smaller ΔG than NA. Measurements of the binding probability at increasing contact time between the scanning force microscopy force probe and the surface allow an estimation of KD, which is found to be three times as large for HA than for NA. This suggests a stronger interaction for NA-SA than for HA-SA. The biological implications in regard to virus binding to the host cell and the release of new virions from the host cell are discussed. Journal Article Biophysical Journal 116 6 1037 1048 Elsevier BV 0006-3495 19 3 2019 2019-03-19 10.1016/j.bpj.2019.01.041 http://dx.doi.org/10.1016/j.bpj.2019.01.041 COLLEGE NANME Chemistry COLLEGE CODE CHEM Swansea University We are grateful for financial support within the SFB765 granted by the Deutsche Forschungsgemeinschaft. 2024-01-02T11:55:09.7077593 2023-11-01T10:40:44.3159874 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry Valentin Reiter-Scherer 1 Jose Luis Cuellar-Camacho 2 Sumati Bhatia 0000-0002-5123-4937 3 Rainer Haag 4 Andreas Herrmann 5 Daniel Lauster 6 Jürgen P. Rabe 7
title Force Spectroscopy Shows Dynamic Binding of Influenza Hemagglutinin and Neuraminidase to Sialic Acid
spellingShingle Force Spectroscopy Shows Dynamic Binding of Influenza Hemagglutinin and Neuraminidase to Sialic Acid
Sumati Bhatia
title_short Force Spectroscopy Shows Dynamic Binding of Influenza Hemagglutinin and Neuraminidase to Sialic Acid
title_full Force Spectroscopy Shows Dynamic Binding of Influenza Hemagglutinin and Neuraminidase to Sialic Acid
title_fullStr Force Spectroscopy Shows Dynamic Binding of Influenza Hemagglutinin and Neuraminidase to Sialic Acid
title_full_unstemmed Force Spectroscopy Shows Dynamic Binding of Influenza Hemagglutinin and Neuraminidase to Sialic Acid
title_sort Force Spectroscopy Shows Dynamic Binding of Influenza Hemagglutinin and Neuraminidase to Sialic Acid
author_id_str_mv a6b1181ebdbe42bd03b24cbdb559d082
author_id_fullname_str_mv a6b1181ebdbe42bd03b24cbdb559d082_***_Sumati Bhatia
author Sumati Bhatia
author2 Valentin Reiter-Scherer
Jose Luis Cuellar-Camacho
Sumati Bhatia
Rainer Haag
Andreas Herrmann
Daniel Lauster
Jürgen P. Rabe
format Journal article
container_title Biophysical Journal
container_volume 116
container_issue 6
container_start_page 1037
publishDate 2019
institution Swansea University
issn 0006-3495
doi_str_mv 10.1016/j.bpj.2019.01.041
publisher Elsevier BV
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/10.1016/j.bpj.2019.01.041
document_store_str 0
active_str 0
description The influenza A virus infects target cells through multivalent interactions of its major spike proteins, hemagglutinin (HA) and neuraminidase (NA), with the cellular receptor sialic acid (SA). HA is known to mediate the attachment of the virion to the cell, whereas NA enables the release of newly formed virions by cleaving SA from the cell. Because both proteins target the same receptor but have antagonistic functions, virus infection depends on a properly tuned balance of the kinetics of HA and NA activities for viral entry to and release from the host cell. Here, dynamic single-molecule force spectroscopy, based on scanning force microscopy, was employed to determine these bond-specific kinetics, characterized by the off rate koff, rupture length xβ and on rate kon, as well as the related free-energy barrier ΔG and the dissociation constant KD. Measurements were conducted using surface-immobilized HA and NA of the influenza A virus strain A/California/04/2009 and a novel, to our knowledge, synthetic SA-displaying receptor for functionalization of the force probe. Single-molecule force spectroscopy at force loading rates between 100 and 50,000 pN/s revealed most probable rupture forces of the protein-SA bond in the range of 10–100 pN. Using an extension of the widely applied Bell-Evans formalism by Friddle, De Yoreo, and co-workers, it is shown that HA features a smaller xβ, a larger koff and a smaller ΔG than NA. Measurements of the binding probability at increasing contact time between the scanning force microscopy force probe and the surface allow an estimation of KD, which is found to be three times as large for HA than for NA. This suggests a stronger interaction for NA-SA than for HA-SA. The biological implications in regard to virus binding to the host cell and the release of new virions from the host cell are discussed.
published_date 2019-03-19T11:55:11Z
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