Crystal structure of a platelet-agglutinating factor isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus).
Platelet glycoprotein Ib (GPIb)-binding proteins (GPIb-BPs) from snake venoms are usually C-type lectins, which target specific sites of GPIbalpha 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 GPIbalpha agonist with a binding site distinct from that of flavocetin-A (a snake venom GPIbalpha antagonist) on GPIbalpha, 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 A (1 A=0.1 nm) resolution, which shows an interesting crystal packing of six-layer cylinders of doughnut-shaped molecules. The four alphabeta 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 Lys102, Lys108, Lys109 and Arg123 in the alpha-subunit coupled with Lys22, Lys102, Lys116 and Arg117 in the beta-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.
Huang
Kai-Fa
KF
Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei 11529, Taiwan.
Ko
Tzu-Ping
TP
Hung
Chin-Chun
CC
Chu
John
J
Wang
Andrew H-J
AH
Chiou
Shyh-Horng
SH
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology; D003001:Cloning, Molecular; D003435:Crotalid Venoms / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000819:agonists* / Q000037:antagonists & inhibitors; D030162:Reptilian Proteins; D017386:Sequence Homology, Amino Acid; D017841:Trimeresurus; D014757:Viper Venoms / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology
D002352:Carrier Proteins; D003435:Crotalid Venoms; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex; D030162:Reptilian Proteins; D014757:Viper Venoms; C402798:flavocetin A; C485097:mucrocetin protein, Trimeresurus mucrosquamatus