7pmu

Crystal structure of native Iripin-8

spinqualitylabelsall models 7pmu, resolution 1.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7pmu is a 1 chain structure with sequence from Ixodes ricinus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.89Å Ligands: P6G, PEG, PG4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0K8RNR1_IXORI Publication Abstract from PubMed 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 A 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. Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement.,Kotal J, Polderdijk SGI, Langhansova H, Ederova M, Martins LA, Berankova Z, Chlastakova A, Hajdusek O, Kotsyfakis M, Huntington JA, Chmelar J Int J Mol Sci. 2021 Aug 31;22(17). pii: ijms22179480. doi: 10.3390/ijms22179480. PMID:34502392 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serpin 3D structures

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