Browsing by Subject "Cryoelectron tomography"

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    Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein
    (Nature Research, 2023-02-04) 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; Ingeniería de la Información y las Comunicaciones
    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.