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