Qinghaienin, a novel anticoagulation protein from the hard tick Haemaphysalis qinghaiensis, inhibits the activation of factor XII by competing for anionic surfaces.

Salivary proteins of ticks can inhibit host hemostatic and inflammatory responses during the blood-sucking process of the parasites. A cDNA sequence, Hq021, was identified from a cDNA library of Haemaphysalis qinghaiensis. Hq021 encodes a mature protein containing 182 amino acids with a molecular mass of 20.5 kDa. The protein is rich in basic amino acids (lysine and arginine) at its C-terminus. Identification of no homologous proteins in databases suggested its novelty. A recombinant protein expressed with the cDNA in Escherichia coli could prolong the activated partial thromboplastin time (aPTT) of human plasma. We designated this basic tail-protein as Qinghaienin. Although Qinghaienin did not inhibit the amidolytic activities of some coagulation factors, it dose-dependently inhibited the generation of FXIIa, FXIa and kallikrein in plasma in the presence of silica-based aPTT reagent. By competing with FXII for the negatively-charged binding sites, Qinghaienin inhibited the activation of the zymogen and the coagulation processes. These findings suggest that Qinghaienin plays a critical role in both anticoagulation and anti-inflammatory processes during tick feeding and could serve as a potential candidate for the developing tick-derived anticoagulants.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gao Jinliang reports financial support was provided by National Natural Science Foundation of China (Contract No. 81760375). Gao Jinliang reports financial support was provided by National Natural Science Foundation of China (Contract No. 82360406). Gao Jinliang reports financial support was provided by Natural Science Foundation of Inner Mongolia Autonomous Region of China (Contract No. 2021MS08063). Chen Kaiting reports financial support was provided by Natural Science Foundation of Inner Mongolia Autonomous Region of China (Contract No. 2023QN08005). Gao Jinliang reports financial support was provided by the Science and Technology Innovation Guiding Project of Inner Mongolia (2021). He Xiaofei reports financial support was provided by Education Department of Inner Mongolia Autonomous Region of China (Contract No. S20231198Z). Gao Jinliang, She Zhanfei, Gao Dongbing, Chen Kaiting, He Xiaofei, Guang Hui, Cao Meina, Zhao Wenbin, Bai Mengdie, Yang Yinran, Su Muya and Ma Linyuan has patent #A tick-derived anticoagulation protein Qinghaienin and its encoding gene as well as its application in anticoagulation,Patent No. ZL 202310665559.5 licensed to Gao Jinliang, She Zhanfei, Gao Dongbing, Chen Kaiting, He Xiaofei, Guang Hui, Cao Meina, Zhao Wenbin, Bai Mengdie, Yang Yinran, Su Muya and Ma Linyuan. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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