The Peptide Derived from erbB2 Auto-Inhibitor Herstatin Shared in the Same Epitope and Function with Functional Antibody 2C4
The Peptide Derived from erbB2 Auto-Inhibitor Herstatin Shared in the Same Epitope and Function with Functional Antibody 2C4
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erbB2 自动抑制剂 Herstatin 衍生的肽与功能性抗体 2C4 具有相同的表位和功能
DOI：
10.1007/s12033-011-9454-y
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发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
吕明
中科院分区：
文献类型：
--
作者：
吕明
先前的研究已经表明，HER 2的不同表位表现出不同的功能，并且抗体2C 4结合的表位在HER 2和HER家族的其他受体之间形成异二聚体中起作用。在这项研究中，我们使用计算机建模来确定HER 2的C-末端79个氨基酸的herstatin（命名为HSTC 79）结合的表位与2C 4结合的表位相似。在此基础上，在大肠杆菌中表达了融合GST的重组HSTC 79，并通过亲和层析进行了纯化。实验分析表明，HSTC 79确实与HER 2特异性结合，并且HSTC 79鉴定的HER 2表位与2C 4鉴定的表位接近。此外，HSTC 79抑制HER 2过表达细胞的生长。这些结果突出了这样一个事实，即HER 2的结合位点结构和某些关键残基可能非常有助于理解蛋白质的生物学作用，并为设计新型HER 2抑制剂提供见解。
Previous studies have shown that different epitopes of HER2 exhibit distinct functions and that the epitope bound by the antibody 2C4 plays a role in formation of hetereodimers between HER2 and other receptors of the HER family. In this study, we used computer modeling to determine that the epitope of HER2 which the C-terminal 79 amino acids of herstatin (named HSTC79) binds is similar to that bound by 2C4. Based on these theoretical results, recombinant HSTC79 fused with GST was expressed inEscherichia coliand purified by affinity chromatography. Experimental analysis showed that HSTC79 did specifically bind to HER2 and that the epitope of HER2 identified by HSTC79 was near that identified by 2C4. Furthermore, HSTC79 inhibited the growth of HER2-overexpressing cells. These results highlight the fact that the binding site architecture and certain key residues of HER2 may be very helpful for understanding the protein’s biological role and providing insights for designing novel inhibitors of HER2.
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影响因子：
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