Related Experiment Video
Updated: May 22, 2025
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High-throughput Confocal Imaging of Quantum Dot-Conjugated SARS-CoV-2 Spike Trimers to Track Binding and Endocytosis in HEK293T Cells
Published on: April 21, 2022
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SARS CoV-2 spike adopts distinct conformational ensembles in situ
Biorxiv : the Preprint Server for Biology
|March 17, 2025
Summary
Recombinant Spike (S) proteins used in vaccines differ dynamically from native SARS-CoV-2 S. Virus-like particles reveal native S has altered dynamics, impacting vaccine epitope display.
Area of Science:
- Virology
- Structural Biology
- Vaccinology
Background:
- Engineered recombinant Spike (S) proteins are crucial for vaccine development and structural studies of SARS-CoV-2.
- Current vaccines, based on recombinant S, offer short-term protection that wanes with emerging variants.
- Recombinant S may not fully represent the native structure and dynamics of S on the virus surface.
Purpose of the Study:
- To compare the conformational dynamics of native, membrane-embedded SARS-CoV-2 Spike (S) protein with engineered recombinant S.
- To investigate the influence of auxiliary viral proteins and membrane environment on S dynamics.
- To assess the implications of these dynamics for vaccine design and epitope accessibility.
Main Methods:
- Utilized virus-like particles (VLPs) displaying full-length S with auxiliary proteins (E, M, N) in a native membrane environment.
- Employed Amide Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS) to analyze protein conformational dynamics.
- Compared HDX-MS data from VLP-displayed S with data from engineered recombinant S.
Main Results:
- Virus-like particle (VLP) displayed S exhibits altered interprotomer contacts compared to recombinant S, due to auxiliary proteins and membrane anchoring.
- Decreased conformational dynamics were observed in the S2 subunit and at interprotomer contact sites in VLP S.
- Minimal differences in dynamics were found in the N-terminal domain (NTD) and receptor-binding domain (RBD) between VLP S and recombinant S.
Conclusions:
- Engineered recombinant S, while useful for structural determination, may not accurately reflect the intrinsic conformational dynamics of native SARS-CoV-2 S.
- The presence of auxiliary proteins and membrane anchoring significantly influences S conformational dynamics.
- Understanding these differences is critical for developing next-generation vaccines with broader and more durable protection, potentially targeting epitopes beyond NTD and RBD.
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