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dc.contributor.authorKotál, Jan
dc.contributor.authorPolderdijk, Stéphanie GI
dc.contributor.authorLanghansová, Helena
dc.contributor.authorEderová, Monika
dc.contributor.authorMartins, Larissa A
dc.contributor.authorBeránková, Zuzana
dc.contributor.authorChlastáková, Adéla
dc.contributor.authorHajdušek, Ondřej
dc.contributor.authorKotsyfakis, Michail
dc.contributor.authorHuntington, Jim
dc.contributor.authorChmelař, Jindřich
dc.date.accessioned2021-11-23T00:30:20Z
dc.date.available2021-11-23T00:30:20Z
dc.date.issued2021-08-31
dc.identifier.issn1661-6596
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330943
dc.description.abstractTick saliva is a rich source of antihemostatic, anti-inflammatory, and immunomodulatory molecules that actively help the tick to finish its blood meal. Moreover, these molecules facilitate the transmission of tick-borne pathogens. Here we present the functional and structural characterization of Iripin-8, a salivary serpin from the tick Ixodes ricinus, a European vector of tick-borne encephalitis and Lyme disease. Iripin-8 displayed blood-meal-induced mRNA expression that peaked in nymphs and the salivary glands of adult females. Iripin-8 inhibited multiple proteases involved in blood coagulation and blocked the intrinsic and common pathways of the coagulation cascade in vitro. Moreover, Iripin-8 inhibited erythrocyte lysis by complement, and Iripin-8 knockdown by RNA interference in tick nymphs delayed the feeding time. Finally, we resolved the crystal structure of Iripin-8 at 1.89 Å resolution to reveal an unusually long and rigid reactive center loop that is conserved in several tick species. The P1 Arg residue is held in place distant from the serpin body by a conserved poly-Pro element on the P' side. Several PEG molecules bind to Iripin-8, including one in a deep cavity, perhaps indicating the presence of a small-molecule binding site. This is the first crystal structure of a tick serpin in the native state, and Iripin-8 is a tick serpin with a conserved reactive center loop that possesses antihemostatic activity that may mediate interference with host innate immunity.
dc.format.mediumElectronic
dc.languageeng
dc.publisherMDPI AG
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleIxodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement.
dc.typeArticle
prism.issueIdentifier17
prism.publicationDate2021
prism.publicationNameInt J Mol Sci
prism.volume22
dc.identifier.doi10.17863/CAM.78387
dcterms.dateAccepted2021-08-26
rioxxterms.versionofrecord10.3390/ijms22179480
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-08-31
dc.contributor.orcidKotál, Jan [0000-0002-5644-1468]
dc.contributor.orcidPolderdijk, Stéphanie GI [0000-0002-4210-6677]
dc.contributor.orcidMartins, Larissa A [0000-0001-8127-6276]
dc.contributor.orcidChlastáková, Adéla [0000-0003-0277-140X]
dc.contributor.orcidKotsyfakis, Michail [0000-0002-7526-1876]
dc.contributor.orcidHuntington, Jim [0000-0003-0076-7204]
dc.contributor.orcidChmelař, Jindřich [0000-0002-7089-6143]
dc.identifier.eissn1422-0067
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-08-31


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International