Multimerization- and glycosylation-dependent receptor binding of SARS-CoV-2 spike proteins.
PLoS Pathog
; 17(2): e1009282, 2021 02.
Article
in English
| MEDLINE | ID: covidwho-1069635
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
Receptor binding studies on sarbecoviruses would benefit from an available toolkit of recombinant spike proteins, or domains thereof, that recapitulate receptor binding properties of native viruses. We hypothesized that trimeric Receptor Binding Domain (RBD) proteins would be suitable candidates to study receptor binding properties of SARS-CoV-1 and -2. Here we created monomeric and trimeric fluorescent RBD proteins, derived from adherent HEK293T, as well as in GnTI-/- mutant cells, to analyze the effect of complex vs high mannose glycosylation on receptor binding. The results demonstrate that trimeric, complex glycosylated proteins are superior in receptor binding compared to monomeric and immaturely glycosylated variants. Although differences in binding to commonly used cell lines were minimal between the different RBD preparations, substantial differences were observed when respiratory tissues of experimental animals were stained. The RBD trimers demonstrated distinct ACE2 expression profiles in bronchiolar ducts and confirmed the higher binding affinity of SARS-CoV-2 over SARS-CoV-1. Our results show that complex glycosylated trimeric RBD proteins are attractive to analyze sarbecovirus receptor binding and explore ACE2 expression profiles in tissues.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Protein Multimerization
/
Spike Glycoprotein, Coronavirus
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
Topics:
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
PLoS Pathog
Year:
2021
Document Type:
Article
Affiliation country:
Journal.ppat.1009282
Similar
MEDLINE
...
LILACS
LIS