Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata

0345741 - BC 2011 RIV GB eng J - Journal Article
Salát, Jiří - Paesen, G.C. - Řezáčová, Pavlína - Kotsyfakis, Michalis - Kovářová, Zuzana - Šanda, Miloslav - Majtán, J. - Grunclová, Lenka - Horká, Helena - Andersen, J. F. - Brynda, Jiří - Horn, Martin - Nunn, M. A. - Kopáček, Petr - Kopecký, Jan - Mareš, Michael
Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata.
Biochemical Journal. Roč. 429, č. 1 (2010), s. 103-112. ISSN 0264-6021. E-ISSN 1470-8728
R&D Projects: GA AV ČR KJB500960702; GA AV ČR IAA600960811; GA ČR(CZ) GAP207/10/2183; GA MŠMT(CZ) LC06009
Institutional research plan: CEZ:AV0Z60220518; CEZ:AV0Z40550506; CEZ:AV0Z50520514
Keywords : cathepsin * cystatin * Ornithodoros moubata * parasite * peptidase inhibitor
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 5.016, year: 2010

Using proteomic analysis, the cystatin OmC2 was demonstrated in the saliva of the soft tick Ornithodoros moubata. A structural, biochemical and biological characterization of this peptidase inhibitor was undertaken in the present study. Recombinant OmC2 was screened against a panel of physiologically relevant peptidases and was found to be an effective broad-specificity inhibitor of cysteine cathepsins, including endopeptidases (cathepsins L and S) and exopeptidases (cathepsins B, C and H). The crystal structure of OmC2 was determined at a resolution of 2.45 angstrom (1 angstrom = 0.1 nm) and was used to describe the structure inhibitory activity relationship. The biological impact of OmC2 was demonstrated both in vitro and in vivo. OmC2 affected the function of antigen-presenting mouse dendritic cells by reducing the production of the pro-inflammatory cytokines tumour necrosis factor alpha and interleukin-12, and proliferation of antigen-specific CD4(+) T-cells.
Permanent Link: http://hdl.handle.net/11104/0186942