邱式鴻2006-07-252018-07-062006-07-252018-07-062004-07-31http://ntur.lib.ntu.edu.tw//handle/246246/10251蛇毒中的血小板醣蛋白Ib (GPIb) 之結合蛋白通常屬於C類植物凝血素，它們會與 GPIbα 結合於特定的位置且引發不同的血小板效應。在此我們提出一個從台灣 龜殼花純化得的四聚合血小板凝集因子(分子量為121.1千道耳吞)---稱為 mucrocetin。雖然 mucrocetin 與 flavocetin 這兩個蛇毒凝血素有極高的序列相似 性 ( 94.6 ％ )，但卻與 GPIbα 結合於不同的位置。在此 mucrocetin 的晶體結 構已被解出至解析度2.8Å，它呈現一六層甜甜圈狀的有趣晶體堆積。這四個αβ- 異質二聚體藉由內部αβ間頭尾相接的雙硫鍵穩定而排列成一獨特的四方環構 造。在進一步細部地比較 mucrocetin 和 flavocetin-A 的結構後，我們可推測在 結合的凹側表面不同的電荷分布可能是造成不同血小板效應的原因。Mucrocetin 結合面上獨特的正電區是主要造成血小板凝集活性的區域，此區由 α 次單元的 賴氨酸 102、108、109、精氨酸 123 以及 β 次單元的賴氨酸 22、102、116 精 氨酸 117 所組成。因此，可想而知地，此有趣之蛇毒因子與 GPIb-IX-V 複合物 結合將成為血小板凝集研究中一有效的工具。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.application/pdf111381 bytesapplication/pdfzh-TW國立臺灣大學生化科學研究所snake venomlectin-like proteinplateletglycoprotein Ibmucrocetinflavocetin-Areporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/10251/1/922311B002107.pdf