Structural Characterization of Coronavirus Spike Proteins
Summary
The coronavirus spike glycoprotein is a trimeric assembly that mediates host cell recognition and membrane fusion. Each protomer comprises an S1 subunit, which engages cellular receptors via a receptor-binding domain (RBD), and an S2 subunit, which undergoes dramatic refolding to drive membrane merger. Structural studies have captured both prefusion and postfusion conformations, revealing critical features such as heptad repeat (HR) regions, glycan shielding and dynamic opening and closing of the RBD. Conformational plasticity balances receptor affinity with immune evasion, while allosteric interdomain crosstalk regulates transitions between states. High-resolution methods including cryogenic electron microscopy and X-ray crystallography have underpinned vaccine design, therapeutic antibody development and pan-coronavirus countermeasure strategies.
Research from Nature Portfolio
Recent structural analysis of a common cold coronavirus spike demonstrated that engagement of a sialoglycan receptor by the S1A domain triggers an allosteric cascade, shifting S1B domains into an open, receptor-accessible state. Cryo-EM and molecular dynamics simulations revealed how this glycan-induced opening primes the spike for subsequent protein receptor binding and membrane fusion.
Engineering efforts have focused on the conserved S2 fusion subunit of SARS-CoV-2, introducing interprotomer disulfide bonds to lock trimers in a prefusion S2-only conformation. Structural characterisation confirmed stability of the locked prefusion state, and immunisation studies in mice elicited broadly neutralising responses against diverse sarbecoviruses, informing next-generation pan-coronavirus vaccine design.
Structural Characterization of Coronavirus Spike Proteins publication trend
The graph below shows the total number of articles in structural characterization of coronavirus spike proteins across all publications each year (not limited to Nature Index journals).
Technical terms
Cryogenic electron microscopy (cryo-EM): A technique for determining near-atomic structures of macromolecules by rapid freezing and imaging with an electron beam.
Prefusion conformation: The structural state of the spike before membrane fusion, stabilised in vaccine constructs to present neutralising epitopes.
Receptor-binding domain (RBD): The region within S1 that recognises and binds to host cell receptors, undergoing “up” and “down” conformational changes.
Heptad repeat (HR) regions: Coiled-coil segments in S2 that assemble into a six-helix bundle during postfusion refolding to drive membrane merger.
Allosteric interdomain crosstalk: Communication between distinct domains of the spike that regulates transitions between closed and open conformations upon ligand binding.
References
- Sialoglycan binding triggers spike opening in a human coronavirus. Nature (2023).
- Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge. Nature Communications (2024).
- Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLOS Pathogens (2018).
- The human coronavirus HCoV-229E S-protein structure and receptor binding. eLife (2019).
- Broadly neutralizing antibodies target the coronavirus fusion peptide. Science (2022).
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