What's Behind the Flexibility of the Spike Proteins in SARS-CoV-2

Following my last post, I recently read a paper which also investigated the Spike Protein of SARS-CoV-2 virions, though focused on the stalk protein which connects S to the viral membrane. In this paper, the researcher took a further analysis into the flexibility of the spikes and the freedom of movement of the spike heads. They used Cryo-electron tomography to acquire the imaging data, while applied molecular dynamic (MD) simulations to identify the sources of the flexibility (Turoňová et al., 2020). Their results, as can be concluded in figure.1, revealed the three hinges (hip, knee and ankle) exist in the stalk region, providing the required bending capacity (Turoňová et al., 2020), which is required for the transformation between open and closed formation of the Spike proteins (Ke et al., 2020). The researchers suggest that the hinges may facilitate the scanning of the host cell surface by the viral spikes; they also shown that the flexibility of S was only found in the prefusion conformation but not in postfusion (Turoňová et al., 2020). I think this direction of research provides useful knowledge that enhances our understanding of the function of the virion, as well as implications for therapeutic targets.

Figure.1 The Model of Spike protein, shown in red are three chains of S, and in blue are N-glycosylation.  (Taken from : Turoňová et al., 2020, page 8)

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Figure.2 MD simulation snapshots mapped to tomograms, showing that the shorter spike proteins are associated with a stronger bending of the hinges. (Taken from: Turoňová et al., 2020, page 9)

References:

Ke, Z., Oton, J., Qu, K. et al. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature (2020). https://doi.org/10.1038/s41586-020-2665-2

Turoňová B, Sikora M, Schürmann C, et al. In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges [published online ahead of print, 2020 Aug 18]. Science. 2020;eabd5223. doi:10.1126/science.abd5223