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| TH：识别牛虻唾液腺中新型蛋白 |
| 添加时间：2011-08-11 17:02:54 浏览次数：1574
来源：中科院昆明动物研究所
作者：中科院昆明动物研究所
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牛虻（中药材名虻虫）为专性吸血昆虫，也是传统的抗血栓中药材，在多种抗血栓中成药生产中被用作原料。近年来，中国科学院昆明动物研究所赖仞研究员领导的课题组围绕牛虻成功吸血的分子机制和发挥抗血栓的物质基础等问题对其开展了较为系统的研究，从牛虻唾液腺中识别了多种功能活性蛋白或多肽(MCP 2008, 7:582-90; MCP 2009, 8:2071-9;Dev Comp Immunol 2008;32:1242-7; Toxicon 2010;55:45-51;Allergy 2011, 66:101-9)。
最近，该课题组与美国国立卫生研究院（NIH）的Jose教授和Ivo博士合作，从牛虻唾液腺中识别了一类新型去整合素家族蛋白，该蛋白通过作用于膜受体aIIbb3以及aVbb从而显著地抑制血小板聚集和抑制血管生成。
该工作提供了一类新型的抗血栓或血管生成抑制剂类抗肿瘤药物候选分子。
此项工作目前已正式发表于《血栓形成与止血》（Thrombosis and Haemostasis）（2011;105:1032-45），研究得到了国家自然科学基金项目和科技部973项目的经费支持。（生物谷Bioon.com）
生物谷推荐原文出处：
Thrombosis and Haemostasis DOI: 10.1160/TH11-01-0029
A novel family of RGD-containing disintegrins (Tablysin-15) from the salivary gland of the horsefly Tabanus yao targets αIIbβ3 or αVβ3 and inhibits platelet aggregation and angiogenesis
D. Ma, X. Xu, S. An, H. Liu, X. Yang, J. F. Andersen, Y. Wang, F. Tokumasu, J. M. C. Ribeiro, I. M. B. Francischetti , R. Lai
A novel family of RGD-containing molecules (Tablysin-15) has been molecularly characterised from the salivary gland of the haematophagous horsefly Tabanus yao. Tablysin-15 does not share primary sequence homology to any disintegrin discovered so far, and displays an RGD motif in the N-terminus of the molecule. It is also distinct from disintegrins from Viperidae since its mature form is not released from a metalloproteinase precursor. Tablysin-15 exhibits high affinity binding for platelet αIIbβ3 and endothelial cell αVβ3 integrins, but not for α5β1 or α2β1. Accordingly, it blocks endothelial cell adhesion to vitronectin (IC50 ~1 nM) and marginally to fibronectin (IC50 ~1 μM), but not to collagen. It also inhibits fibroblast growth factor (FGF)-induced endothelial cell proliferation, and attenuates tube formation in vitro. In platelets, Tablysin-15 inhibits aggregation induced by collagen, ADP and convulxin, and prevents static platelet adhesion to immobilised fibrinogen. In addition, solid-phase assays and flow cytometry demonstrates that αIIbβ3 binds to Tablysin-15. Moreover, immobilised Tablysin-15 supports platelet adhesion by a mechanism which was blocked by anti-integrin αIIbβ3 monoclonal antibody (e.g. abciximab) or by EDTA. Furthermore, Tablysin-15 dose-dependently attenuates thrombus formation to collagen under flow. Consistent with these findings, Tablysin-15 displays antithrombotic properties in vivo suggesting that it is a useful tool to block αIIbβ3, or as a prototype to develop antithrombotics. The RGD motif in the unique sequence of Tablysin-15 represents a novel template for studying the structure-function relationship of the disintegrin family of inhibitors.
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