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TitleDirect Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 620, Year 2023
Publish dateFeb 4, 2023
AuthorsChristopher Cyrus Kuhn / Nirakar Basnet / Satish Bodakuntla / Pelayo Alvarez-Brecht / Scott Nichols / Antonio Martinez-Sanchez / Lorenzo Agostini / Young-Min Soh / Junichi Takagi / Christian Biertümpfel / Naoko Mizuno /
PubMed 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 ...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 αβ. 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.
External linksNat Commun / PubMed:36739444 / PubMed Central
MethodsEM (tomography) / EM (single particle)
Resolution3.56 Å
Structure data

EMDB-26794: Tomogram of platelet filopodia in presence of SARS-CoV-2 spike protein
Method: EM (tomography)

EMDB-26796: Tomogram of platelet protrusion with microtubule in presence of SARS-CoV-2 spike protein
Method: EM (tomography)

EMDB-26798: SARS-CoV-2 spike protein closed conformation
Method: EM (single particle) / Resolution: 3.56 Å

Source
  • Homo sapiens (human)
  • Severe acute respiratory syndrome coronavirus 2

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