Structural and biochemical characterization of the novel serpin Iripin‐5 from Ixodes ricinus. Issue 9 (2nd September 2021)

• Record Type: Journal Article
• Authors: Kascakova, Barbora; Kotal, Jan; Martins, Larissa Almeida; Berankova, Zuzana; Langhansova, Helena; Calvo, Eric; Crossley, Joel A.; Havlickova, Petra; Dycka, Filip; Prudnikova, Tatyana; Kuty, Michal; Kotsyfakis, Michail; Chmelar, Jindrich; Kuta Smatanova, Ivana
• Is Part Of: Acta crystallographica. Volume 77:Issue 9(2021)
• Page Start: 1183
• Page End: 1196
• Publication Date: 2021-09-02
• Subjects: serpins -- serine protease inhibitors -- Iripin‐5 -- X‐ray structure -- Ixodes ricinus -- tick saliva; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; Molecular biology -- Periodicals; Molecular structure -- Periodicals; Biomolecules -- Structure -- Periodicals; Cytology -- Periodicals; Biomolecules -- Structure; Crystallography; Cytology; Molecular biology; Molecular structure; X-ray crystallography; Periodicals; 548
• DOI: 10.1107/S2059798321007920
• Languages: English
• ISSNs: 2059-7983

Abstract

Abstract : Biochemical, structural and functional characterization of Iripin‐5, the most abundant serpin from the salivary glands of Ixodes ricinus, together with interface analysis, revealed the possible interactions with proteases that are necessary to explain the mechanism of action of serpins. Abstract : Iripin‐5 is the main Ixodes ricinus salivary serpin, which acts as a modulator of host defence mechanisms by impairing neutrophil migration, suppressing nitric oxide production by macrophages and altering complement functions. Iripin‐5 influences host immunity and shows high expression in the salivary glands. Here, the crystal structure of Iripin‐5 in the most thermodynamically stable state of serpins is described. In the reactive‐centre loop, the main substrate‐recognition site of Iripin‐5 is likely to be represented by Arg342, which implies the targeting of trypsin‐like proteases. Furthermore, a computational structural analysis of selected Iripin‐5–protease complexes together with interface analysis revealed the most probable residues of Iripin‐5 involved in complex formation.