Biotoxin Units of Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, 32# Jiaochangdonglu, Kunming 650223, Yunnan, China.
Toxicon. 2010 Jan;55(1):45-51. doi: 10.1016/j.toxicon.2009.06.038. Epub 2009 Jul 25.
The Ag5 proteins are the most abundant and immunogenic proteins in the venom secretory ducts of stinging insects. An antigen 5-like protein (named tabRTS) composed of 221 amino acid residues was purified and characterized from the salivary glands of the horsefly, Tabanus yao (Diptera, Tabanidae). Its cDNA was cloned from the cDNA library of the horsefly's salivary gland. TabRTS containing the SCP domain (Sc7 family of extracellular protein domain) was found in insect antigen 5 proteins. More interestingly, there is an Arg-Thr-Ser (RTS) disintegrin motif at the C-terminus of tabRTS. The RTS motif is positioned in a loop bracketed by cysteine residues as those found in RTS-disintegrins of Crotalidae and Viperidae snake venoms, which act as angiogenesis inhibitors. Endothelial Cell Tube formation assay in vitro and chicken chorioallantoic membrane (CAM) angiogenesis assay in vivo were performed as to investigate the effect of tabRTS on angiogenesis. It was found that tabRTS could significantly inhibit angiogenesis in vitro and in vivo. Anti-alpha(1)beta(1) monoclonal antibody could dose-dependently inhibit the anti-angiogenic activity of tabRTS. This result indicated that tabRTS possibly targets the alpha(1)beta(1) integrin to exert the anti-angiogenic activity as snake venom RTS-/KTS-disintegrins do. The current work revealed the first angiogenesis inhibitor protein containing RTS motif from invertebrates, a possible novel type of RTS-disintegrin.
Ag5 蛋白是蜇刺昆虫毒液分泌管中最丰富和最具免疫原性的蛋白。从虻科虻属（双翅目）的唾液腺中纯化并鉴定了一种由 221 个氨基酸残基组成的抗原 5 样蛋白（命名为 tabRTS）。它的 cDNA 是从虻唾液腺 cDNA 文库中克隆的。TabRTS 含有 SCP 结构域（细胞外蛋白结构域 Sc7 家族），存在于昆虫抗原 5 蛋白中。更有趣的是，tabRTS 的 C 末端有一个 Arg-Thr-Ser（RTS）解整合素基序。该 RTS 基序位于半胱氨酸残基之间的环内，与眼镜蛇科和蝰蛇科蛇毒液中的 RTS-解整合素相同，它们作为血管生成抑制剂。进行了体外内皮细胞管形成试验和体内鸡胚绒毛尿囊膜（CAM）血管生成试验，以研究 tabRTS 对血管生成的影响。结果表明，tabRTS 可显著抑制体外和体内的血管生成。抗α1β1 单克隆抗体可剂量依赖性抑制 tabRTS 的抗血管生成活性。这一结果表明，tabRTS 可能通过靶向α1β1 整合素来发挥抗血管生成活性，就像蛇毒 RTS-/KTS-解整合素一样。目前的工作揭示了第一个含有 RTS 基序的来自无脊椎动物的血管生成抑制剂蛋白，可能是一种新型的 RTS 解整合素。
