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Varani_2023_MDPI_ijms_Analytical Ultracentrifugation
Journal article

Analytical ultracentrifugation detects quaternary rearrangements and antibody-induced conformational selection of the SARS-CoV-2 spike trimer

  • Guerrini, Giuditta European Commission, Joint Research Centre (JRC), Ispra, Italy
  • Mehn, Dora European Commission, Joint Research Centre (JRC), Ispra, Italy
  • Fumagalli, Francesco European Commission, Joint Research Centre (JRC), Ispra, Italy
  • Gioria, Sabrina European Commission, Joint Research Centre (JRC), Ispra, Italy
  • Pedotti, Mattia ORCID Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Simonelli, Luca Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Bianchini, Filippo ORCID Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Robbiani, Davide F. ORCID Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Varani, Luca ORCID Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Calzolai, Luigi European Commission, Joint Research Centre (JRC), Ispra, Italy
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  • 2023
Published in:
  • International journal of molecular sciences. - 2023, vol. 24, no. 19, p. 14875
SARS-CoV-2
Spike
Trimer
Antibody
AUC
Analytical ultracentrifugation
Sedimentation
Conformation
English Analytical ultracentrifugation (AUC) analysis shows that the SARS-CoV-2 trimeric Spike (S) protein adopts different quaternary conformations in solution. The relative abundance of the “open” and “close” conformations is temperature-dependent, and samples with different storage temperature history have different open/close distributions. Neutralizing antibodies (NAbs) targeting the S receptor binding domain (RBD) do not alter the conformer populations; by contrast, a NAb targeting a cryptic conformational epitope skews the Spike trimer toward an open conformation. The results highlight AUC, which is typically applied for molecular mass determination of biomolecules as a powerful tool for detecting functionally relevant quaternary protein conformations.
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Language
  • English
Classification
Medicine
License
CC BY
Open access status
gold
Identifiers
Persistent URL
https://n2t.net/ark:/12658/srd1332081
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