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Publication Abstract from PubMed

During feeding, a tick's mouthpart penetrates the host's skin and damages tissues and small blood vessels, triggering the extrinsic coagulation and lectin complement pathways. To elude these defense mechanisms, ticks secrete multiple anticoagulant proteins and complement system inhibitors in their saliva. Here we characterized the inhibitory activities of the homologous tick salivary proteins TSLPI, Salp14, and Salp9Pac from Ixodida scapularis in the coagulation cascade and the lectin complement pathway. All three proteins inhibited binding of mannan-binding lectin (MBL) to the polysaccharide mannan, preventing the activation of the lectin complement pathway. In contrast, only Salp14 showed an appreciable effect on coagulation by prolonging the lag time of thrombin generation. We found that the anticoagulant properties of Salp14 are governed by its basic tail region, which resembles the C-terminus of tissue factor pathway inhibitor alpha (TFPIalpha) and blocks the assembly and/or activity of the prothrombinase complex in the same way. Moreover, the Salp14 protein tail contributes to the inhibition of the lectin complement pathway via interaction with MBL-associated serine proteases. Furthermore, we identified BaSO4-adsorbing protein 1 (BSAP1) isolated from the tick Ornithodoros savignyi as a distant homologue of TSLPI/Salp14 proteins and show that it inhibits the lectin complement pathway but not coagulation. The structure of BSAP1, solved here using NMR spectroscopy, indicated that this protein adopts a non-canonical EGF domain-like structural fold, the first such report for tick salivary proteins. These data support a mechanism by which tick saliva proteins simultaneously inhibit both the host coagulation cascade and the lectin complement pathway.

Molecular basis of anticoagulant and anti-complement activity of the tick salivary protein Salp14 and its homologues.,Denisov SS, Ippel JH, Castoldi E, Hackeng TM, Dijkgraaf I J Biol Chem. 2021 Jun 9:100865. doi: 10.1016/j.jbc.2021.100865. PMID:34118237^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.