tetano
Editor, Senior Moderator
iScience
. 2021 Oct 13;103272.
doi: 10.1016/j.isci.2021.103272. Online ahead of print.
The effect of N- glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor
Chuncui Huang[SUP] 1 2 [/SUP], Zeshun Tan[SUP] 1 3 [/SUP], Keli Zhao[SUP] 1 3 [/SUP], Wenjun Zou[SUP] 1 3 [/SUP], Hui Wang[SUP] 4 3 [/SUP], Huanyu Gao[SUP] 1 [/SUP], Shiwei Sun[SUP] 4 3 [/SUP], Dongbo Bu[SUP] 4 3 [/SUP], Wengang Chai[SUP] 5 [/SUP], Yan Li[SUP] 1 3 2 [/SUP]
Affiliations
Abstract
The densely glycosylated spike (S) protein highly exposed on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) surface mediates host cell entry by binding to the receptor angiotensin-converting enzyme 2 (ACE2). However, the role of glycosylation has not been fully understood. In this study, we investigated the effect of different N-glycosylation of S1 protein on its binding to ACE2. Using real-time surface plasmon resonance assay the negative effects were demonstrated by the considerable increase of binding affinities of de-N-glycosylated S1 proteins produced from three different expression systems including baculovirus-insect, Chinese hamster ovarian and two variants of human embryonic kidney 293 cells. Molecular dynamic simulations of the S1 protein-ACE2 receptor complex revealed the steric hinderance and Coulombic repulsion effects of different types of N-glycans on the S1 protein interaction with ACE2. The results should contribute to future pathological studies of SARS-CoV-2 and therapeutic development of Covid-19, particularly using recombinant S1 proteins as models.
Keywords: Binding affinity; N-glycosylation; S1 protein; Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); Spike protein.
. 2021 Oct 13;103272.
doi: 10.1016/j.isci.2021.103272. Online ahead of print.
The effect of N- glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor
Chuncui Huang[SUP] 1 2 [/SUP], Zeshun Tan[SUP] 1 3 [/SUP], Keli Zhao[SUP] 1 3 [/SUP], Wenjun Zou[SUP] 1 3 [/SUP], Hui Wang[SUP] 4 3 [/SUP], Huanyu Gao[SUP] 1 [/SUP], Shiwei Sun[SUP] 4 3 [/SUP], Dongbo Bu[SUP] 4 3 [/SUP], Wengang Chai[SUP] 5 [/SUP], Yan Li[SUP] 1 3 2 [/SUP]
Affiliations
- PMID: 34661088
- PMCID: PMC8513389
- DOI: 10.1016/j.isci.2021.103272
Abstract
The densely glycosylated spike (S) protein highly exposed on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) surface mediates host cell entry by binding to the receptor angiotensin-converting enzyme 2 (ACE2). However, the role of glycosylation has not been fully understood. In this study, we investigated the effect of different N-glycosylation of S1 protein on its binding to ACE2. Using real-time surface plasmon resonance assay the negative effects were demonstrated by the considerable increase of binding affinities of de-N-glycosylated S1 proteins produced from three different expression systems including baculovirus-insect, Chinese hamster ovarian and two variants of human embryonic kidney 293 cells. Molecular dynamic simulations of the S1 protein-ACE2 receptor complex revealed the steric hinderance and Coulombic repulsion effects of different types of N-glycans on the S1 protein interaction with ACE2. The results should contribute to future pathological studies of SARS-CoV-2 and therapeutic development of Covid-19, particularly using recombinant S1 proteins as models.
Keywords: Binding affinity; N-glycosylation; S1 protein; Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); Spike protein.