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Analytical Ultracentrifugation Detects Quaternary Rearrangements and Antibody-Induced Conformational Selection of the SARS-CoV-2 Spike Trimer
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 ha...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573103/ https://www.ncbi.nlm.nih.gov/pubmed/37834322 http://dx.doi.org/10.3390/ijms241914875 |
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author | Guerrini, Giuditta Mehn, Dora Fumagalli, Francesco Gioria, Sabrina Pedotti, Mattia Simonelli, Luca Bianchini, Filippo Robbiani, Davide F. Varani, Luca Calzolai, Luigi |
author_facet | Guerrini, Giuditta Mehn, Dora Fumagalli, Francesco Gioria, Sabrina Pedotti, Mattia Simonelli, Luca Bianchini, Filippo Robbiani, Davide F. Varani, Luca Calzolai, Luigi |
author_sort | Guerrini, Giuditta |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10573103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105731032023-10-14 Analytical Ultracentrifugation Detects Quaternary Rearrangements and Antibody-Induced Conformational Selection of the SARS-CoV-2 Spike Trimer Guerrini, Giuditta Mehn, Dora Fumagalli, Francesco Gioria, Sabrina Pedotti, Mattia Simonelli, Luca Bianchini, Filippo Robbiani, Davide F. Varani, Luca Calzolai, Luigi Int J Mol Sci Brief Report 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. MDPI 2023-10-03 /pmc/articles/PMC10573103/ /pubmed/37834322 http://dx.doi.org/10.3390/ijms241914875 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Brief Report Guerrini, Giuditta Mehn, Dora Fumagalli, Francesco Gioria, Sabrina Pedotti, Mattia Simonelli, Luca Bianchini, Filippo Robbiani, Davide F. Varani, Luca Calzolai, Luigi Analytical Ultracentrifugation Detects Quaternary Rearrangements and Antibody-Induced Conformational Selection of the SARS-CoV-2 Spike Trimer |
title | Analytical Ultracentrifugation Detects Quaternary Rearrangements and Antibody-Induced Conformational Selection of the SARS-CoV-2 Spike Trimer |
title_full | Analytical Ultracentrifugation Detects Quaternary Rearrangements and Antibody-Induced Conformational Selection of the SARS-CoV-2 Spike Trimer |
title_fullStr | Analytical Ultracentrifugation Detects Quaternary Rearrangements and Antibody-Induced Conformational Selection of the SARS-CoV-2 Spike Trimer |
title_full_unstemmed | Analytical Ultracentrifugation Detects Quaternary Rearrangements and Antibody-Induced Conformational Selection of the SARS-CoV-2 Spike Trimer |
title_short | Analytical Ultracentrifugation Detects Quaternary Rearrangements and Antibody-Induced Conformational Selection of the SARS-CoV-2 Spike Trimer |
title_sort | analytical ultracentrifugation detects quaternary rearrangements and antibody-induced conformational selection of the sars-cov-2 spike trimer |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573103/ https://www.ncbi.nlm.nih.gov/pubmed/37834322 http://dx.doi.org/10.3390/ijms241914875 |
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