Publication: Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein
Authors
Cyrus Kuhn, Christopher ; Basnet, Nirakar ; Bodakuntla, Satish ; Alvarez-Brecht, Pelayo ; Nichols, Scott ; Martínez-Sánchez, Antonio ; Agostini, Lorenzo ; Soh, Young-Min ; Takagi, Junichi ; Biertümpfel, Christian ; Mizuno, Naoko
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Publisher
Nature Research
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DOI
https://doi.org/10.1038/s41467-023-36279-5
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info:eu-repo/semantics/article
Description
© 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in Nature Communications. To access the final edited and published work see https://doi.org/10.1038/s41467-023-36279-5
Abstract
SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic. Its high pathogenicity is due to SARS-CoV-2 spike protein (S protein) contacting host-cell receptors. A critical hallmark of COVID-19 is the occurrence of coagulopathies. Here, we report the direct observation of the interactions between S protein and platelets. Live imaging shows that the S protein triggers platelets to deform dynamically, in some cases, leading to their irreversible activation. Cellular cryo-electron tomography reveals dense decorations of S protein on the platelet surface, inducing filopodia formation. Hypothesizing that S protein binds to filopodia-inducing integrin receptors, we tested the binding to RGD motif-recognizing platelet integrins and find that S protein recognizes integrin αvβ3. Our results infer that the stochastic activation of platelets is due to weak interactions of S protein with integrin, which can attribute to the pathogenesis of COVID-19 and the occurrence of rare but severe coagulopathies.
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Citation
Nature Communications 2023, 14:620
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by/4.0/