Analytical Ultracentrifugation Detects Quaternary Rearrangements and Antibody-Induced Conformational Selection of the SARS-CoV-2 Spike Trimer.
Giuditta GuerriniDora MehnFrancesco FumagalliSabrina GioriaMattia PedottiLuca SimonelliFilippo BianchiniDavide F RobbianiLuca VaraniLuigi CalzolaiPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- sars cov
- molecular dynamics simulations
- single molecule
- minimally invasive
- binding protein
- respiratory syndrome coronavirus
- molecular dynamics
- protein protein
- magnetic resonance
- amino acid
- high glucose
- advanced non small cell lung cancer
- antibiotic resistance genes
- magnetic resonance imaging
- zika virus
- dengue virus
- transcription factor
- monoclonal antibody
- dna binding
- crystal structure