Dimiconin, a novel coagulation inhibitor from the kissing bug, Triatoma dimidiata, a vector of Chagas disease

J Exp Biol. 2012 Oct 15;215(Pt 20):3597-602. doi: 10.1242/jeb.074211. Epub 2012 Jul 5.

Abstract

Sequence analysis of a Triatoma dimidiata salivary gland cDNA library resulted in the identification of two transcripts (Td60 and Td101) homologous to triabin, an inhibitor of thrombin in Triatoma pallidipennis saliva. In the present study, a recombinant protein of Td60, designated dimiconin, was expressed in Escherichia coli and its activity was characterized. The resulting protein inhibited the intrinsic but not extrinsic blood coagulation pathway, suggesting that dimiconin is not a thrombin inhibitor. Measurement of the enzymatic activity of coagulation factors using chromogenic substrates revealed that dimiconin efficiently inhibited factor XIIa (FXIIa) activity in a dose-dependent manner. In addition, pre-incubation of dimiconin with FXII effectively inhibited FXIIa activity whereas dimiconin did not affect already activated FXIIa, indicating that dimiconin inhibits the activation of FXII but not the enzymatic activity of FXIIa. These results show that dimiconin is an inhibitor of the contact phase initiated by FXII activation in the blood coagulation cascade, which differs from the bioactivity of triabin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anticoagulants*
  • Base Sequence
  • Blood Coagulation / drug effects*
  • Chagas Disease / transmission
  • Factor XIIa / antagonists & inhibitors*
  • Insect Proteins / genetics
  • Insect Proteins / metabolism*
  • Insect Proteins / pharmacology*
  • Insect Vectors / metabolism
  • Molecular Sequence Data
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Salivary Glands / metabolism
  • Salivary Proteins and Peptides / genetics
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Triatoma / genetics
  • Triatoma / metabolism*

Substances

  • Anticoagulants
  • Insect Proteins
  • Recombinant Proteins
  • Salivary Proteins and Peptides
  • triabin
  • Factor XIIa