Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:433 |
|---|---|
| Enthalten in: |
Journal of molecular biology - 433(2021), 4 vom: 19. Feb., Seite 166762 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Allen, Joel D [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 16.02.2021 Date Revised 30.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jmb.2020.166762 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM319053733 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM319053733 | ||
| 003 | DE-627 | ||
| 005 | 20240330234724.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jmb.2020.166762 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1356.xml |
| 035 | |a (DE-627)NLM319053733 | ||
| 035 | |a (NLM)33340519 | ||
| 035 | |a (PII)S0022-2836(20)30687-2 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Allen, Joel D |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 16.02.2021 | ||
| 500 | |a Date Revised 30.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ACE2 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a glycan engineering | |
| 650 | 4 | |a glycosylation | |
| 650 | 4 | |a surface plasmon resonance | |
| 650 | 7 | |a Polysaccharides |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 650 | 7 | |a ACE2 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 650 | 7 | |a Angiotensin-Converting Enzyme 2 |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 700 | 1 | |a Watanabe, Yasunori |e verfasserin |4 aut | |
| 700 | 1 | |a Chawla, Himanshi |e verfasserin |4 aut | |
| 700 | 1 | |a Newby, Maddy L |e verfasserin |4 aut | |
| 700 | 1 | |a Crispin, Max |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of molecular biology |d 1960 |g 433(2021), 4 vom: 19. Feb., Seite 166762 |w (DE-627)NLM000006777 |x 1089-8638 |7 nnns |
| 773 | 1 | 8 | |g volume:433 |g year:2021 |g number:4 |g day:19 |g month:02 |g pages:166762 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jmb.2020.166762 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 433 |j 2021 |e 4 |b 19 |c 02 |h 166762 | ||