Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement

0554204 - BC 2022 RIV CH eng J - Journal Article
Kotál, Jan - Polderdijk, S. - Langhansová, H. - Ederova, M. - Martins, Larissa Almeida - Beránková, Z. - Chlastáková, A. - Hajdušek, Ondřej - Kotsyfakis, Michalis - Huntington, J. - Chmelař, J.
Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement.
International Journal of Molecular Sciences. Roč. 22, č. 17 (2021), č. článku 9480. E-ISSN 1422-0067
R&D Projects: GA MŠMT(CZ) EF16_019/0000759
Institutional support: RVO:60077344
Keywords : tsetse thrombin inhibitor * tick saliva * anticoagulant activity * blood-coagulation * immune-response * protein * disease * expression * peptide * cloning * blood coagulation * crystal structure * Ixodes ricinus * parasite * saliva * serpin * tick
OECD category: Microbiology
Impact factor: 6.208, year: 2021
Method of publishing: Open access
https://www.mdpi.com/1422-0067/22/17/9480

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 angstrom 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.
Permanent Link: http://hdl.handle.net/11104/0328823