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Altered O-glycosylation Level of SARS-CoV-2 Spike Protein by Host O-glycosyltransferase Strengthens Its Trimeric Structure
Zhijue Xu; Xin Ku; Jiaqi Tian; Han Zhang; Jingli Hou; Can Zhang; Jingjing Shi; Yang Li; Hiroyuki Kaji; Sheng-ce Tao; Atsushi Kuno; Wei Yan; Lin-Tai Da; Yan Zhang.
Afiliação
  • Zhijue Xu; Shanghai Jiao Tong University
  • Xin Ku; Shanghai Jiao Tong University
  • Jiaqi Tian; Shanghai Jiao Tong University
  • Han Zhang; Shanghai Jiao Tong University
  • Jingli Hou; Shanghai Jiao Tong University
  • Can Zhang; Shanghai Jiao Tong University
  • Jingjing Shi; Shanghai Jiao Tong University
  • Yang Li; Shanghai Jiao Tong University
  • Hiroyuki Kaji; National Institute of Advanced Industrial Science and Technology (AIST)
  • Sheng-ce Tao; Shanghai Jiao Tong University
  • Atsushi Kuno; National Institute of Advanced Industrial Science and Technology (AIST)
  • Wei Yan; Shanghai Jiao Tong University
  • Lin-Tai Da; Shanghai Jiao Tong University
  • Yan Zhang; Shanghai Jiao Tong University
Preprint em En | PREPRINT-BIORXIV | ID: ppbiorxiv-438614
ABSTRACT
The trimeric spike protein (S) mediates host-cell entry and membrane fusion of SARS-CoV-2. S protein is highly glycosylated, whereas its O-glycosylation is still poorly understood. Herein, we site-specifically examine the O-glycosylation of S protein through a mass spectrometric approach with HCD-triggered-ETD model. We identify 15 high-confidence O-glycosites and at least 10 distinct O-glycan structures on S protein. Peptide microarray assays prove that human ppGalNAc-T6 actively participates in O-glycosylation of S protein. Importantly, the upregulation of ppGalNAc-T6 expression can profoundly enhance the O-glycosylation level by generating new O-glycosites and increasing both O-glycan heterogeneity and intensities. Further molecular dynamics simulations reveal that the O-glycosylation on the protomer-interface regions, which are mainly modified by ppGalNAc-T6, can potentially stabilize the trimeric S protein structure. Our work provides deep molecular insights of how viral infection harnesses the host O-glycosyltransferases to dynamically regulate the O-glycosylation level of the viral envelope protein responsible for membrane fusion.
Licença
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Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Idioma: En Ano de publicação: 2021 Tipo de documento: Preprint
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Idioma: En Ano de publicação: 2021 Tipo de documento: Preprint