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Identification of 22 N-glycosites on spike glycoprotein of SARS-CoV-2 and accessible surface glycopeptide motifs: Implications for vaccination and antibody therapeutics.
Zhou, Dapeng; Tian, Xiaoxu; Qi, Ruibing; Peng, Chao; Zhang, Wen.
  • Zhou D; Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, China.
  • Tian X; Shanghai Pudong New Area Mental Health Center affiliated with Tongji University School of Medicine, 165 Sanlin Road, Shanghai 200124, China.
  • Qi R; National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Science, 333 Haike Road, Shanghai 201210, China.
  • Peng C; Innovation Team of Small Animal Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, 518 Ziyue Road, Shanghai 200241, China.
  • Zhang W; National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Science, 333 Haike Road, Shanghai 201210, China.
Glycobiology ; 31(1): 69-80, 2021 01 09.
Article in English | MEDLINE | ID: covidwho-592209
ABSTRACT
Coronaviruses hijack human enzymes to assemble the sugar coat on their spike glycoproteins. The mechanisms by which human antibodies may recognize the antigenic viral peptide epitopes hidden by the sugar coat are unknown. Glycosylation by insect cells differs from the native form produced in human cells, but insect cell-derived influenza vaccines have been approved by the US Food and Drug Administration. In this study, we analyzed recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein secreted from BTI-Tn-5B1-4 insect cells, by trypsin and chymotrypsin digestion followed by mass spectrometry analysis. We acquired tandem mass spectrometry (MS/MS) spectrums for glycopeptides of all 22 predicted N-glycosylated sites. We further analyzed the surface accessibility of spike proteins according to cryogenic electron microscopy and homolog-modeled structures and available antibodies that bind to SARS-CoV-1. All 22 N-glycosylated sites of SARS-CoV-2 are modified by high-mannose N-glycans. MS/MS fragmentation clearly established the glycopeptide identities. Electron densities of glycans cover most of the spike receptor-binding domain of SARS-CoV-2, except YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQ, similar to a region FSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQ in SARS-CoV-1. Other surface-exposed domains include those located on central helix, connecting region, heptad repeats and N-terminal domain. Because the majority of antibody paratopes bind to the peptide portion with or without sugar modification, we propose a snake-catching model for predicted paratopes a minimal length of peptide is first clamped by a paratope and sugar modifications close to the peptide either strengthen or do not hinder the binding.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Glycopeptides / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Glycobiology Journal subject: Biochemistry Year: 2021 Document Type: Article Affiliation country: Glycob

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Glycopeptides / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Glycobiology Journal subject: Biochemistry Year: 2021 Document Type: Article Affiliation country: Glycob