Gao Li-Hua, Hu Xian-Wen, Chen Wei, Xu Jun-Jie, Zhao Jian, Chen Hui-Peng
Beijing Institute of Biotechnology, Beijing 100071, China.
Sheng Wu Gong Cheng Xue Bao. 2005 Sep;21(5):826-31.
ATR-Fc is a fusion protein consisting of extracellular domain of human anthrax toxin receptor (ATR) and a fragment (hinge, CH2, and CH3 domains) of the Fc of human IgG1. The aim of ATR-Fc expression is to get an antibody-like molecule binding to protective antigen (PA), a component of anthrax toxins, this fusion protein may compete with cell surface receptor for PA binding, and block the transport of lethal factor (LF) and edema factor (EF) into cells, thereby act as an antitoxin to prevent and treat anthrax infection. A DNA fragment encoding N-terminal amino acids 1-227 of ATR and human IgG1 Fc was inserted into the Hind III and Not I sites of pcDNA3.1 to generate the eukaryotic vector pcDNA3.1/ATR-Fc for expression of ATR-Fc fusion protein. Using lipofectine-mediated gene transfer technique, pcDNA3.1/ATR-Fc was transfected into CHO-K1 cells. After selected with G418, a recombinant CHO cell line, ATR-Fc-1D5, whose expression level was about 10 - 15 microg/(10(6) cells x d), was established. The recombinant protein expressed by the ATR-Fc-1D5 cells was purified with protein A chromatography. The experimental results demonstrated a direct and specific interaction between ATR-Fc and PA assessed by ELISA.
ATR-Fc是一种融合蛋白,由人炭疽毒素受体(ATR)的细胞外结构域和人IgG1的Fc片段(铰链区、CH2和CH3结构域)组成。表达ATR-Fc的目的是获得一种与炭疽毒素的一种成分保护性抗原(PA)结合的抗体样分子,这种融合蛋白可能与细胞表面受体竞争PA结合,并阻止致死因子(LF)和水肿因子(EF)进入细胞,从而作为一种抗毒素来预防和治疗炭疽感染。将编码ATR的N端1-227个氨基酸和人IgG1 Fc的DNA片段插入pcDNA3.1的Hind III和Not I位点,以产生用于表达ATR-Fc融合蛋白的真核载体pcDNA3.1/ATR-Fc。使用脂质体介导的基因转移技术,将pcDNA3.1/ATR-Fc转染到CHO-K1细胞中。经G418筛选后,建立了一个重组CHO细胞系ATR-Fc-1D5,其表达水平约为10 - 15微克/(10^6个细胞×天)。用蛋白A层析法纯化ATR-Fc-1D5细胞表达的重组蛋白。实验结果通过ELISA证明了ATR-Fc与PA之间存在直接和特异性的相互作用。