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Cold sensitivity of the SARS-CoV-2 spike ectodomain
Edwards, R. J., Mansouri, K., Stalls, V., Manne, K., Watts, B., Parks, R., Janowska, K., Gobeil, S. M. C., Kopp, M., Li, D., Lu, X., Mu, Z., Deyton, M., Oguin, T. H., Sprenz, J., Williams, W., Saunders, K. O., Montefiori, D., Sempowski, G. D., ... Acharya, P. (2021). Cold sensitivity of the SARS-CoV-2 spike ectodomain. Nature Structural Biology, 28(2), 128-131. https://doi.org/10.1038/s41594-020-00547-5
The SARS-CoV-2 spike (S) protein, a primary target for COVID-19 vaccine development, presents its receptor binding domain in two conformations, the receptor-accessible 'up' or receptor-inaccessible 'down' states. Here we report that the commonly used stabilized S ectodomain construct '2P' is sensitive to cold temperatures, and this cold sensitivity is abrogated in a 'down' state-stabilized ectodomain. Our findings will impact structural, functional and vaccine studies that use the SARS-CoV-2 S ectodomain.