Site-specific steric control of SARS-COV-2 spike glycosylation

DOI: 10.1021/acs.biochem.1c00279

Authors: Joel D. Allen (University of Southampton) , Himanshi Chawla (University of Southampton) , Firdaus Samsudin (Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR)) , Lorena Zuzic (Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR); Manchester Institute of Biotechnology, The University of Manchester) , Aishwary Tukaram Shivgan (Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR); National University of Singapore) , Yasunori Watanabe (University of Southampton) , Wan-Ting He (The Scripps Research Institute) , Sean Callaghan (The Scripps Research Institute) , Ge Song (The Scripps Research Institute) , Peter Yong (The Scripps Research Institute) , Philip J. M. Brouwer (University of Amsterdam) , Yutong Song (Tsinghua University; Beijing Advanced Innovation Center for Structural Biology and Frontier Research Center for Biological Structure) , Yongfei Cai (Boston Children’s Hospital) , Helen M. E. Duyvesteyn (The Wellcome Centre for Human Genetics, University of Oxford) , Tomas Malinauskas (The Wellcome Centre for Human Genetics, University of Oxford) , Joeri Kint (ExcellGene SA) , Paco Pino (ExcellGene SA) , Maria J. Wurm (ExcellGene SA) , Martin Frank (Biognos AB) , Bing Chen (Boston Children’s Hospital; Harvard Medical School) , David I. Stuart (The Wellcome Centre for Human Genetics, University of Oxford; Diamond Light Source) , Rogier W. Sanders (University of Amsterdam; Weill Medical College of Cornell University) , Raiees Andrabi (The Scripps Research Institute) , Dennis R. Burton , Sai Li (Tsinghua University; Beijing Advanced Innovation Center for Structural Biology and Frontier Research Center for Biological Structure) , Peter J. Bond (Technology and Research (A*STAR); National University of Singapore) , Max Crispin (University of Southampton)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Biochemistry

State: Published (Approved)
Published: July 2021

Abstract: A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation. Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells. We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure. Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans. These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.

Journal Keywords: Peptides and proteins; Carbohydrates; Genetics; Chemical biology; Post-translational modification

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Technical Areas:

Added On: 05/07/2021 08:22

Discipline Tags:

Vaccines Pathogens Infectious Diseases Health & Wellbeing Biochemistry Chemistry Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags: