Visualization and functional annotation of coronavirus spike protein glycoshields
Journal of Biological Chemistry
; 299(3 Supplement):S542, 2023.
Article
in English
| EMBASE | ID: covidwho-2315442
ABSTRACT
Spike proteins of coronaviruses are highly glycosylated and responsible for host recognition and viral entry. The glycans provide a camouflaging shield to help coronaviruses evade host immunity and, in some cases, modulate functional domain structures and dynamics pertinent to host recognition. However, the glycans are chemically and conformationally heterogeneous, making it challenging to determine the chemical compositions and conformations quantitatively. Combining cryo-electron microscopy, mass spectrometry, and molecular modeling, we systematically characterize a panel of spike protein variants of human and animal coronaviruses, including those of the variants of concern of SARS-CoV-2. We have established a robust workflow to quantify the heterogeneity of individual N-glycans by mass spectrometry. We also demonstrated the ability to visualize long glycan structures directly in regions where the dynamics are restricted. In places where the N-glycans are too dynamic, their structural information is generally lost after extended cryo-EM data processing that aims to achieve high resolution. To address this issue, we developed a computational tool called GlycoSHIELD to generate ensembles of glycan conformers to recapitulate the fuzzy structures that are in quantitative agreement with the experimental cryo-EM data. The ability to generate fully glycosylated spike protein models enables the prediction of hitherto unknown receptor and antibody binding sites. This work was supported by Academia Sinica intramural fund, an Academia Sinica Career Development Award, Academia Sinica to STDH (AS-CDA-109- L08), an Infectious Disease Research Supporting Grant to STDH (AS-IDR- 110-08), and the Ministry of Science and Technology (MOST), Taiwan (MOST 109-3114-Y-001-001, MOST 110-2113-M-001- 050-MY3 and MOST 110-2311-B-001-013-MY3) to STDH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
animal experiment; animal model; antibody combining site; antigen binding; awards and prizes; career; communicable disease; conference abstract; cryoelectron microscopy; human; mass spectrometry; molecular model; nonhuman; prediction; receptor binding; Severe acute respiratory syndrome coronavirus 2; Taiwan; variant of concern; workflow; coronavirus spike glycoprotein; endogenous compound; glycan; unclassified drug
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Journal of Biological Chemistry
Year:
2023
Document Type:
Article
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