Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Waldeyerstr. 15, 48149 Münster, Germany.
Toxins (Basel). 2019 Mar 1;11(3):136. doi: 10.3390/toxins11030136.
Snake venoms contain an astounding variety of different proteins. Among them are numerous C-type lectin family members, which are grouped into classical Ca- and sugar-binding lectins and the non-sugar-binding snake venom C-type lectin-related proteins (SV-CLRPs), also called snaclecs. Both groups share the robust C-type lectin domain (CTLD) fold but differ in a long loop, which either contributes to a sugar-binding site or is expanded into a loop-swapping heterodimerization domain between two CLRP subunits. Most C-type lectin (-related) proteins assemble in ordered supramolecular complexes with a high versatility of subunit numbers and geometric arrays. Similarly versatile is their ability to inhibit or block their target molecules as well as to agonistically stimulate or antagonistically blunt a cellular reaction triggered by their target receptor. By utilizing distinct interaction sites differentially, SV-CLRPs target a plethora of molecules, such as distinct coagulation factors and receptors of platelets and endothelial cells that are involved in hemostasis, thrombus formation, inflammation and hematogenous metastasis. Because of their robust structure and their high affinity towards their clinically relevant targets, SV-CLRPs are and will potentially be valuable prototypes to develop new diagnostic and therapeutic tools in medicine, provided that the molecular mechanisms underlying their versatility are disclosed.
蛇毒中含有种类繁多的不同蛋白质。其中有许多 C 型凝集素家族成员，它们分为经典的 Ca 和糖结合凝集素以及非糖结合蛇毒 C 型凝集素相关蛋白（SV-CLRPs），也称为 snaclecs。这两组都具有坚固的 C 型凝集素结构域（CTLD）折叠，但在长环上有所不同，该长环要么有助于形成糖结合位点，要么扩展为两个 CLRP 亚基之间的环交换异二聚化结构域。大多数 C 型凝集素（相关）蛋白以有序的超分子复合物组装，具有很高的亚基数量和几何排列的多功能性。同样多功能的是它们抑制或阻断其靶分子的能力，以及激动性刺激或拮抗其靶受体触发的细胞反应的能力。通过利用不同的相互作用位点，SV-CLRPs 靶向多种分子，例如涉及止血、血栓形成、炎症和血液转移的不同凝血因子和血小板及内皮细胞受体。由于其坚固的结构和对其临床相关靶标的高亲和力，SV-CLRPs 是并且将有可能成为开发医学中新型诊断和治疗工具的有价值原型，前提是揭示其多功能性的分子机制。
