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 language | English |
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Pages (from-to) | 399-407 |
Number of pages | 9 |
Journal | Biochemical Journal |
Volume | 378 |
Issue number | 2 |
DOIs | |
Publication status | Published - Mar 1 2004 |
Externally published | Yes |
Keywords
- Flavocetin-A
- Lectin-like protein
- Mucrocetin
- Platelet glycoprotein Ib
- Snake venom
- Trimeresurus mucrosquamatus
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology