Crystal structure of a platelet-agglutinating factor isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus)

Kai Fa Huang, K. O. Tzu-Ping, Chin Chun Hung, John Chu, Andrew H.J. Wang, Shyh Horng Chiou

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Platelet glycoprotein Ib (GPIb)-binding proteins (GPIb-BPs) from snake venoms are usually C-type lectins, which target specific sites of GPIbα and elicit distinct effects on platelets. In the present paper, we report a tetrameric platelet-agglutinating factor (molecular mass 121.1 kDa), termed mucrocetin, purified from the venom of Taiwan habu (Trimeresurus mucrosquamatus). Mucrocetin is a GPIbα agonist with a binding site distinct from that of flavocetin-A (a snake venom GPIbα antagonist) on GPIbα, in spite of the high sequence identity (94.6%) between the two venom lectins. The crystal structure of mucrocetin was solved and refined to 2. 8 Å (1 Å = 0.1 nm) resolution, which shows an interesting crystal packing of six-layer cylinders of doughnut-shaped molecules. The four αβ heterodimers are arranged in an unusual square-shaped ring stabilized by four interdimer 'head-to-tail' disulphide bridges. Detailed structural comparison between mucrocetin and flavocetin-A suggests that their disparate platelet effects are probably attributable to different charge distributions on the putative concave binding surface. A unique positively charged patch on the binding surface of mucrocetin, formed by Lys 102, Lys108, Lys109 and Arg123 in the α-subunit coupled with Lys22, Lys102, Lys 116 and Arg117 in the β-subunit, appears to be the primary determinant of its platelet-agglutinating activity. Conceivably, this interesting venom factor may provide a useful tool to study platelet agglutination by binding to the GPIb-IX-V complex.

Original languageEnglish
Pages (from-to)399-407
Number of pages9
JournalBiochemical Journal
Volume378
Issue number2
DOIs
Publication statusPublished - Mar 1 2004
Externally publishedYes

Keywords

  • Flavocetin-A
  • Lectin-like protein
  • Mucrocetin
  • Platelet glycoprotein Ib
  • Snake venom
  • Trimeresurus mucrosquamatus

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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