Crystal structure of von Willebrand factor A1 domain complexed with snake venom, bitiscetin: Insight into glycoprotein Ibα binding mechanism induced by snake venom proteins

Nobuo Maita, Kenji Nishio, Etsuko Nishimoto, Taei Matsui, Yasuo Shikamoto, Takashi Morita, J. Evan Sadler, Hiroshi Mizuno

研究成果: Contribution to journalArticle査読

69 被引用数 (Scopus)

抄録

Bitiscetin, a platelet adhesion inducer isolated from venom of the snake Bitis arietans, activates the binding of the von Willebrand factor (VWF) A1 domain to glycoprotein Ib (GPIb) in vitro. This activation requires the formation of a bitiscetin-VWF A1 complex, suggesting an allosteric mechanism of action. Here, we report the crystal structure of bitiscetin-VWF A1 domain complex solved at 2.85 Å. In the complex structure, helix α5 of VWF A1 domain lies on a concave depression on bitiscetin, and binding sites are located at both ends of the depression. The binding sites correspond well with those proposed previously based on alanine-scanning mutagenesis (Matsui, T., Hamako, J., Matsushita, T., Nakayama, T., Fujimura, Y., and Titani, K. (2002) Biochemistry 41, 7939-7946). Against our expectations, the structure of the VWF A1 domain bound to bitiscetin does not differ significantly from the structure of the free A1 domain. These results are similar to the case of botrocetin, another snake-derived inducer of platelet aggregation, although the binding modes of botrocetin and bitiscetin are different. The modeled structure of the ternary bitiscetin-VWF A1-GPIb complex suggests that an electropositive surface of bitiscetin may interact with a favorably positioned anionic region of GPIb. These results suggest that snake venom proteins induce VWF A1-GPIbα binding by interacting with both proteins, and not by causing conformational changes in VWF A1.

本文言語英語
ページ(範囲)37777-37781
ページ数5
ジャーナルJournal of Biological Chemistry
278
39
DOI
出版ステータス出版済み - 9 26 2003
外部発表はい

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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