Journal article 460 views
Quantification of Multivalent Interactions between Sialic Acid and Influenza A Virus Spike Proteins by Single-Molecule Force Spectroscopy
,
Sumati Bhatia ,
Valentin Reiter-Scherer,
Daniel Lauster,
Susanne Liese ,
Jürgen P. Rabe ,
Andreas Herrmann ,
Rainer Haag
Journal of the American Chemical Society, Volume: 142, Issue: 28, Pages: 12181 - 12192
Swansea University Author:
Sumati Bhatia
Full text not available from this repository: check for access using links below.
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...
| Published in: | Journal of the American Chemical Society |
|---|---|
| ISSN: | 0002-7863 1520-5126 |
| Published: |
American Chemical Society (ACS)
2020
|
| Online Access: |
Check full text
|
| URI: | https://cronfa.swan.ac.uk/Record/cronfa64865 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| 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 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. |
|---|---|
| Keywords: |
Force spectroscopy, Receptors, Screening assays, Stability, Viruses |
| College: |
Faculty of Science and Engineering |
| Issue: |
28 |
| Start Page: |
12181 |
| End Page: |
12192 |