| Co-Investigator(Kenkyū-buntansha) |
HAMAKO Jiharu Fujita Health University College, Associate Professor, 衛生技術科, 助教授 (80180933)
HAYASHI Nobuhiro Inst.for Comprehensive Med.Sci., Fujita Health University Research Associate, 総合医科学研究所, 助手 (80267955)
MATSUI Taei Inst.for Comprehensive Med.Sci., Fujita Health University Assistant Professor, 総合医科学研究所, 講師 (90183946)
FUJIMURA Yoshihiro Nara Medical University, Professor, 輸血部, 教授 (80118033)
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| Research Abstract |
1) Studies on the isolation and structure-function relationship of snake venom proteins modulating interaction between von Willebrand factor (vWF) and platelets. We have searched, identified and structurally characterized novel snake venom proteins that modulate platelet adhesion and aggregation by interacting with vWF.a) We screened. vWF-binding proteins from 19 species of snake venoms and discovered "bitiscetin", a novel vWF-modulating protein from the venom of Bitis arietans, and "kaouthiagin", a vWF-cleaving metalloproteinase from the venom of Naja kaouthia. We purified the two proteins and determined their complete amino acid sequences. Since the sequence of bitiscetin was not highly homologous to that of botrocetin with a similar activity, we expressed many mutants of A-1 loop of vWF, which binds to it, to identify residues interacting with bitiscetin. The results indicated that bitiscetin interacts with a site not identical but very close to that interacts with botrocetin. Kaout
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hiagin was shown to be composed of metalloproteinase, disintegrin-like and Cys-rich domains. Interestingly, the Cys-rich domain contained a RGD sequence. We demonstrated that both the disintegrin-like and Cys-rich domains have the disintegrin activity using synthetic cyclic peptides. b) We purified a protein termed "mamushigin" from the venom of Agkistrodon halys blomhoffii (Japanese "mamushi") which binds to platelet GPIb to induce the aggregation. We isolated the cDNA clones encoding the α and β chains from the library and predicted the complete amino acid sequences of both the chains. From the same venom, we also isolated and determined the complete amino acid sequence of a serine protease termed halystase which releases bradykinin from kininogen in human plasma.
2) Origin of plasma vWF with ABO blood group antigens. vWF is a unique plasma protein with the blood group antigens. Since those antigens on human plasma vWF are not changed to those of the donors after ABO-mismatched bone marrow transplantation, we concluded that plasma vWF with the blood groups is derived from endothelial cells, but not from megakaryocytes (platelets). Less
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