Thromb Haemost 2017; 117(06): 1031-1039
DOI: 10.1160/TH16-11-0829
Coagulation and Fibrinolysis
Schattauer GmbH

Joannsin, a novel Kunitz-type FXa inhibitor from the venom of Prospirobolus joannsi

Ning Luan
1  Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, China
,
Chunling Zhou
1  Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, China
,
Pengpeng Li
1  Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, China
,
Rose Ombati
2  Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China
4  Sino-African Joint Research Center, CAS, Kunming Institute of Zoology, Kunming, Yunnan, China
5  University of Chinese Academy of Sciences, Beijing, China
,
Xiuwen Yan
1  Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, China
,
Guoxiang Mo
1  Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, China
,
Mingqiang Rong
2  Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China
,
Ren Lai
1  Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, China
2  Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China
5  University of Chinese Academy of Sciences, Beijing, China
,
Zilei Duan
2  Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China
5  University of Chinese Academy of Sciences, Beijing, China
,
Ruiqiang Zheng
3  Intensive Care Unit, Subei People’s Hospital of Jiangsu Province, Yangzhou, Jiangsu, China
› Author Affiliations
Further Information

Publication History

Received: 09 November 2016

Accepted after major revision: 19 February 2017

Publication Date:
07 November 2017 (online)

  

Summary

The repugnatorial glands of millipedes release various defensive chemical secretions. Although varieties of such defensive secretions have been studied, none of them is protein or peptide. Herein, a novel factor Xa (FXa) inhibitor named joannsin was identified and characterised from repugnatorial glands of Prospirobolus joannsi. Joannsin is composed of 72 amino acid residues including six cysteines, which form three intra-molecular disulfide bridges. It is a member of Kunitz-type protease inhibitor family, members of which are also found in the secretory glands of other arthropods. Recombinant joannsin exhibited remarkable inhibitory activity against trypsin and FXa with a Ki of 182.7 ± 14.6 and 29.5 ± 4.7 nM, respectively. Joannsin showed strong anti-thrombosis functions in vitro and in vivo. Joannsin is the first peptide component in millipede repugnatorial glands to be identified and is a potential candidate and/or template for the development of anti-thrombotic agents. These results also indicated that there is Kunitz-type protease inhibitor toxin in millipede repugnatorial glands as in other arthropods secretory glands.

§These authors contributed equally to this paper.