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dc.contributor.authorKilkenny, Mairi L
dc.contributor.authorVeale, Charlotte E
dc.contributor.authorGuppy, Amir
dc.contributor.authorHardwick, Steven W
dc.contributor.authorChirgadze, Dimitri Y
dc.contributor.authorRzechorzek, Neil J
dc.contributor.authorMaman, Joseph D
dc.contributor.authorPellegrini, Luca
dc.date.accessioned2021-11-22T14:33:56Z
dc.date.available2021-11-22T14:33:56Z
dc.date.issued2022-02
dc.date.submitted2021-09-09
dc.identifier.issn0961-8368
dc.identifier.otherpro4220
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330770
dc.description.abstractThe molecular mechanisms that drive the infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the causative agent of coronavirus disease 2019 (COVID-19)-are under intense current scrutiny to understand how the virus operates and to uncover ways in which the disease can be prevented or alleviated. Recent proteomic screens of the interactions between viral and host proteins have identified the human proteins targeted by SARS-CoV-2. The DNA polymerase α (Pol α)-primase complex or primosome-responsible for initiating DNA synthesis during genomic duplication-was identified as a target of nonstructural protein 1 (nsp1), a major virulence factor in the SARS-CoV-2 infection. Here, we validate the published reports of the interaction of nsp1 with the primosome by demonstrating direct binding with purified recombinant components and providing a biochemical characterization of their interaction. Furthermore, we provide a structural basis for the interaction by elucidating the cryo-electron microscopy structure of nsp1 bound to the primosome. Our findings provide biochemical evidence for the reported targeting of Pol α by the virulence factor nsp1 and suggest that SARS-CoV-2 interferes with Pol α's putative role in the immune response during the viral infection.
dc.languageen
dc.publisherWiley
dc.subjectFull‐Length Paper
dc.subjectFull‐Length Papers
dc.subjectcryo‐EM
dc.subjectDNA polymerase α–primase
dc.subjectnsp1
dc.subjectprotein–protein interaction
dc.subjectSARS‐CoV‐2
dc.titleStructural basis for the interaction of SARS-CoV-2 virulence factor nsp1 with DNA polymerase α-primase.
dc.typeArticle
dc.date.updated2021-11-22T14:33:55Z
prism.publicationNameProtein Sci
dc.identifier.doi10.17863/CAM.78213
dcterms.dateAccepted2021-10-28
rioxxterms.versionofrecord10.1002/pro.4220
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidPellegrini, Luca [0000-0002-9300-497X]
dc.identifier.eissn1469-896X
pubs.funder-project-idWellcome Trust (104641/Z/14/Z)
cam.issuedOnline2021-11-12


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