The University of Southampton
University of Southampton Institutional Repository

Subtle influence of ACE2 glycan processing on SARS-CoV-2 recognition

Subtle influence of ACE2 glycan processing on SARS-CoV-2 recognition
Subtle influence of ACE2 glycan processing on SARS-CoV-2 recognition

The severity of SARS-CoV-2 infection is highly variable and yet the molecular basis for this effect remains elusive. One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans. The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated. We therefore sought to investigate whether the glycosylation state of ACE2 impacts the interaction with SARS-CoV-2 viral spike. We generated a panel of engineered ACE2 glycoforms which were analyzed by mass spectrometry to reveal the site-specific glycan modifications. We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction. In contrast, deglycosylation of ACE2 did not influence SARS-CoV-2 binding. Overall, ACE2 glycosylation does not significantly influence viral spike binding. We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding.

0022-2836
Allen, Joel D
c89d5569-7659-4835-b535-c9586e956b3a
Watanabe, Yasunori
8c0ee4af-a293-4de5-9036-3ce2051b380c
Chawla, Himanshi
07b9e983-4c35-4314-999d-fe3222a6c03b
Newby, Maddy L
417cba47-6a6f-42b9-8b9c-640f0518c621
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Allen, Joel D
c89d5569-7659-4835-b535-c9586e956b3a
Watanabe, Yasunori
8c0ee4af-a293-4de5-9036-3ce2051b380c
Chawla, Himanshi
07b9e983-4c35-4314-999d-fe3222a6c03b
Newby, Maddy L
417cba47-6a6f-42b9-8b9c-640f0518c621
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9

Allen, Joel D, Watanabe, Yasunori, Chawla, Himanshi, Newby, Maddy L and Crispin, Max (2020) Subtle influence of ACE2 glycan processing on SARS-CoV-2 recognition. Journal of Molecular Biology, 433 (4), [166762]. (doi:10.1016/j.jmb.2020.166762).

Record type: Article

Abstract

The severity of SARS-CoV-2 infection is highly variable and yet the molecular basis for this effect remains elusive. One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans. The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated. We therefore sought to investigate whether the glycosylation state of ACE2 impacts the interaction with SARS-CoV-2 viral spike. We generated a panel of engineered ACE2 glycoforms which were analyzed by mass spectrometry to reveal the site-specific glycan modifications. We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction. In contrast, deglycosylation of ACE2 did not influence SARS-CoV-2 binding. Overall, ACE2 glycosylation does not significantly influence viral spike binding. We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding.

Text
Subtle Influence - Version of Record
Available under License Creative Commons Attribution.
Download (1MB)

More information

Accepted/In Press date: 11 November 2020
e-pub ahead of print date: 17 December 2020

Identifiers

Local EPrints ID: 446910
URI: http://eprints.soton.ac.uk/id/eprint/446910
ISSN: 0022-2836
PURE UUID: ca00b5d8-42b2-4715-8ce7-269f67aa1eb6
ORCID for Joel D Allen: ORCID iD orcid.org/0000-0003-2547-968X
ORCID for Himanshi Chawla: ORCID iD orcid.org/0000-0001-9828-6593
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 26 Feb 2021 17:30
Last modified: 17 Mar 2024 04:09

Export record

Altmetrics

Contributors

Author: Joel D Allen ORCID iD
Author: Yasunori Watanabe
Author: Himanshi Chawla ORCID iD
Author: Maddy L Newby
Author: Max Crispin ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×