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Multimerization- and glycosylation-dependent receptor binding of SARS-CoV-2 spike proteins.
Bouwman, Kim M; Tomris, Ilhan; Turner, Hannah L; van der Woude, Roosmarijn; Shamorkina, Tatiana M; Bosman, Gerlof P; Rockx, Barry; Herfst, Sander; Snijder, Joost; Haagmans, Bart L; Ward, Andrew B; Boons, Geert-Jan; de Vries, Robert P.
  • Bouwman KM; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
  • Tomris I; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
  • Turner HL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
  • van der Woude R; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
  • Shamorkina TM; Biomolecular Mass Spectrometry and Proteomics, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
  • Bosman GP; Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
  • Rockx B; Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
  • Herfst S; Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Snijder J; Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Haagmans BL; Biomolecular Mass Spectrometry and Proteomics, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
  • Ward AB; Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
  • Boons GJ; Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • de Vries RP; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
PLoS Pathog ; 17(2): e1009282, 2021 02.
Article in English | MEDLINE | ID: covidwho-1069635
Preprint
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ABSTRACT
Receptor binding studies on sarbecoviruses would benefit from an available toolkit of recombinant spike proteins, or domains thereof, that recapitulate receptor binding properties of native viruses. We hypothesized that trimeric Receptor Binding Domain (RBD) proteins would be suitable candidates to study receptor binding properties of SARS-CoV-1 and -2. Here we created monomeric and trimeric fluorescent RBD proteins, derived from adherent HEK293T, as well as in GnTI-/- mutant cells, to analyze the effect of complex vs high mannose glycosylation on receptor binding. The results demonstrate that trimeric, complex glycosylated proteins are superior in receptor binding compared to monomeric and immaturely glycosylated variants. Although differences in binding to commonly used cell lines were minimal between the different RBD preparations, substantial differences were observed when respiratory tissues of experimental animals were stained. The RBD trimers demonstrated distinct ACE2 expression profiles in bronchiolar ducts and confirmed the higher binding affinity of SARS-CoV-2 over SARS-CoV-1. Our results show that complex glycosylated trimeric RBD proteins are attractive to analyze sarbecovirus receptor binding and explore ACE2 expression profiles in tissues.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Multimerization / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Topics: Variants Limits: Animals / Humans Language: English Journal: PLoS Pathog Year: 2021 Document Type: Article Affiliation country: Journal.ppat.1009282

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Multimerization / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Topics: Variants Limits: Animals / Humans Language: English Journal: PLoS Pathog Year: 2021 Document Type: Article Affiliation country: Journal.ppat.1009282