Anticoagulation factor I, a snaclec (snake C-type lectin) from Agkistrodon acutus venom binds to FIX as well as FX: Ca²⁺ induced binding data

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• 作者：Yan Zhang ; Xiaolong Xu ; ^{xuxl@ustc.edu.cn} ; Dengke Shen ; Jiajia Song ; Mingchun Guo ; Xincheng Yan
• 关键词：Agkistrodon acutuss ; ACF I ; Snaclec ; Ca2+ ; Factor IX
• 刊名：Toxicon
• 出版年：2012
• 期刊代码：50_00410101
• 类别：pha
• 出版时间：1 June, 2012
• 卷：59
• 期：7-8
• 页码：718-723
• 文件大小：543 K

摘要

Anticoagulation factor I (ACF I), a snake C-type lectin (snaclec) from the venom of Agkistrodon acutus binds specifically with activated factor X (FXa) in a Ca²⁺-dependent manner and prolongs the blood-clotting time in聽vitro. In this study, the inhibition of the coagulation pathway by ACF I was measured in聽vivo by activated partial thromboplastin time and prothrombin time assays and the binding of ACF I to factor IX (FIX) was investigated by native PAGE and surface plasmon resonance. The results indicate that ACF I inhibits both intrinsic and extrinsic coagulation pathways, but does not inhibit thrombin activity. ACF I also binds FIX in a Ca²⁺-dependent manner and their maximal binding occurs at 0.25 mM Ca²⁺. ACF I has a higher binding-affinity to FIX than to FX. Ca²⁺ is required to maintain in聽vivo function of FIX Gla domain for its recognition of ACF I. However, Ca²⁺ at high concentrations (>0.25 mM) inhibits the binding of ACF I to FIX. Ca²⁺ functions as a switch for the binding between ACF I and FIX. The results suggest that the binding of ACF I with FIX may play a dominant role in the anticoagulation activity of ACF I in聽vivo.