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Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement
J. Kotál, SGI. Polderdijk, H. Langhansová, M. Ederová, LA. Martins, Z. Beránková, A. Chlastáková, O. Hajdušek, M. Kotsyfakis, JA. Huntington, J. Chmelař
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
19-14704Y
Grantová Agentura České Republiky
384 CZ.02.1.01/0.0/0.0/16_019/0000759
European Regional Development Fund
Free Medical Journals od 2000
Freely Accessible Science Journals od 2000
PubMed Central od 2007
Europe PubMed Central od 2007
ProQuest Central od 2000-03-01
Open Access Digital Library od 2000-01-01
Open Access Digital Library od 2007-01-01
Health & Medicine (ProQuest) od 2000-03-01
ROAD: Directory of Open Access Scholarly Resources od 2000
Odkazy
PubMed
34502392
DOI
10.3390/ijms22179480
Knihovny.cz E-zdroje
- MeSH
- aktivace komplementu účinky léků imunologie fyziologie MeSH
- erytrocyty metabolismus MeSH
- exprese genu genetika MeSH
- hemokoagulace účinky léků fyziologie MeSH
- klíště enzymologie genetika metabolismus MeSH
- komplement metabolismus MeSH
- lymeská nemoc MeSH
- nymfa MeSH
- proteiny členovců metabolismus MeSH
- regulace genové exprese genetika MeSH
- serpiny metabolismus ultrastruktura MeSH
- slinné žlázy metabolismus MeSH
- sliny chemie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Tick 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.
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- $a Kotál, Jan $u Department of Medical Biology, Faculty of Science, University of South Bohemia in České Budějovice, Branišovská 1760c, 37005 České Budějovice, Czech Republic $u Laboratory of Genomics and Proteomics of Disease Vectors, Institute of Parasitology, Biology Center CAS, Branišovská 1160/31, 37005 České Budějovice, Czech Republic
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- $a Tick 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.
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