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Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein

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dc.contributor.authorCyrus Kuhn, Christopher
dc.contributor.authorBasnet, Nirakar
dc.contributor.authorBodakuntla, Satish
dc.contributor.authorAlvarez-Brecht, Pelayo
dc.contributor.authorNichols, Scott
dc.contributor.authorMartínez-Sánchez, Antonio
dc.contributor.authorAgostini, Lorenzo
dc.contributor.authorSoh, Young-Min
dc.contributor.authorTakagi, Junichi
dc.contributor.authorBiertümpfel, Christian
dc.contributor.authorMizuno, Naoko
dc.contributor.departmentIngeniería de la Información y las Comunicaciones
dc.date.accessioned2025-01-18T19:38:07Z
dc.date.available2025-01-18T19:38:07Z
dc.date.issued2023-02-04
dc.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
dc.description.abstractSARS-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.
dc.formatapplication/pdfes
dc.format.extent14
dc.identifier.citationNature Communications 2023, 14:620
dc.identifier.doihttps://doi.org/10.1038/s41467-023-36279-5
dc.identifier.issnElectronic: 2041-1723
dc.identifier.urihttp://hdl.handle.net/10201/148744
dc.languageenges
dc.publisherNature Research
dc.relationThe light microscopic data was collected at the NHLBI light microscopy core facility, the flow analysis was performed at the NHLBI flow cytometry core and the cryo-ET data was collected at the MICEF at the National Institutes of Health, USA and at the National Cancer Institute’s National Cryo-EM Facility at the Frederick National Laboratory for Cancer Research under contract HSSN261200800001E. This work used the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov). The following reagents were obtained through BEI Resources, NIAID, NIH: SARS-Related Coronavirus 2, Wuhan-Hu-1 Spike-Pseudotyped Lentivirus, Luc2/ZsGreen, NR-53818. N.M. acknowledges the Intramural Research Program of the National Heart Lung and Blood Institute (1ZIAHL006264 and 1ZIAHL006265), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of National Institutes of Health, USA, for funding.es
dc.relation.publisherversionhttps://www.nature.com/articles/s41467-023-36279-5
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCell polarity
dc.subjectCell signalling
dc.subjectCryoelectron tomography
dc.subjectProteins
dc.titleDirect Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike proteines
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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