The cDNA cloning and molecular characterization of a snake venom platelet glycoprotein Ib-binding protein, mamushigin, from Agkistrodon halys blomhoffii venom

Yoshihiko Sakurai, Yoshihiro Fujimura, Tetsuro Kokubo, Kouji Imamura, Tomihisa Kawasaki, Makoto Handa, Masami Suzuki, Taei Matsui, Koiti Titani, Akira Yoshioka

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54 Citations (Scopus)

Abstract

The entire cDNA sequences of a novel snake venom platelet glycoprotein (GP) Ib-binding protein (BP) composed of an α/β heterodimeric structure, termed mamushigin, from Agkistrodon halys blomhoffii were determined, that include the leader peptides (21/23 amino acid residues) and mature subunits (136/123 amino acid residues). The mature subunits of mamushigin are 37.5% identical, and showed a high degree of similarity (37.7-67.5% identity) with the respective subunits of group VII C-type lectins. The sequences of the leader peptides of the mamusigin subunits showed the highest similarity (α-73.91/β-82.6%) with those of factor IX/X-BP from Trimeresurus flavoridis, and the cleavage site residue in both proteins was the same Ala-1. The GPIb-binding specificity of mamushigin is strongly supported by several lines of evidence, but mamushigin can directly aggregate normal platelets, similar to alboaggregin-B (AL-B). This differs from other GPIb-BP's. In mamushigin-treated platelets, serotonin was not released, and flow cytometric analysis using a monoclonal antibody PAC-1 totally excluded platelet GPIIb/IIIa activation. Mamushigin enhanced platelet aggregation at low-shear stress, and this effect totally disappeared in the presence of GPIb-receptor blockers specific for von Willebrand factor binding, but not by GPIIb/IIIa-receptor blockers. At high-shear stress, mamushigin blocked platelet aggregation in a dose-dependent manner, as seen with other GPIb-BP's. This paper, therefore, describes the cDNA cloning and molecular characterization of mamushigin which has a different effect on platelet aggregation under different shear stress.

Original languageEnglish
Pages (from-to)1199-1207
Number of pages9
JournalThrombosis and Haemostasis
Volume79
Issue number6
DOIs
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Hematology

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