Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Guerrini, Giuditta, Mehn, Dora, Fumagalli, Francesco, Gioria, Sabrina, Pedotti, Mattia, Simonelli, Luca, Bianchini, Filippo, Robbiani, Davide F., Varani, Luca, Calzolai, Luigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785120387588161536
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
work_keys_str_mv AT guerrinigiuditta analyticalultracentrifugationdetectsquaternaryrearrangementsandantibodyinducedconformationalselectionofthesarscov2spiketrimer
AT mehndora analyticalultracentrifugationdetectsquaternaryrearrangementsandantibodyinducedconformationalselectionofthesarscov2spiketrimer
AT fumagallifrancesco analyticalultracentrifugationdetectsquaternaryrearrangementsandantibodyinducedconformationalselectionofthesarscov2spiketrimer
AT gioriasabrina analyticalultracentrifugationdetectsquaternaryrearrangementsandantibodyinducedconformationalselectionofthesarscov2spiketrimer
AT pedottimattia analyticalultracentrifugationdetectsquaternaryrearrangementsandantibodyinducedconformationalselectionofthesarscov2spiketrimer
AT simonelliluca analyticalultracentrifugationdetectsquaternaryrearrangementsandantibodyinducedconformationalselectionofthesarscov2spiketrimer
AT bianchinifilippo analyticalultracentrifugationdetectsquaternaryrearrangementsandantibodyinducedconformationalselectionofthesarscov2spiketrimer
AT robbianidavidef analyticalultracentrifugationdetectsquaternaryrearrangementsandantibodyinducedconformationalselectionofthesarscov2spiketrimer
AT varaniluca analyticalultracentrifugationdetectsquaternaryrearrangementsandantibodyinducedconformationalselectionofthesarscov2spiketrimer
AT calzolailuigi analyticalultracentrifugationdetectsquaternaryrearrangementsandantibodyinducedconformationalselectionofthesarscov2spiketrimer