以毒素及毒素/蛋白水解酵素複合物的結晶構造為基礎對蛇毒毒素作結構─功能的分析(2/3)

Platelet glycoprotein Ib-binding proteins (GPIb-BPs) from snake venoms are usually
C-type lectins, which target on specific sites of GPIb α and elicit distinct effects on
platelets. Here, we report a tetrameric platelet-agglutinating factor (Mr = 121.1 kDa),
termed mucrocetin, purified from the venom of Taiwan habu (Trimeresurus
mucrosquamatus). Mucrocetin is a GPIb agonist with a distinct binding site from that
of flavocetin-A (a snake venom GPIb α antagonist) on GPIb α 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 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
inter-dimer “head-to-tail” disulfide bridges. Detailed structural comparison between
mucrocetin and flavocetin-A suggests that their disparate platelet effects are likely
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 , Lys 108 , Lys 109 and Arg 123 in α-subunit coupled with Lys 22 , Lys 102 , Lys
116 and Arg 117 in 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 GP Ib-IX-V complex.