Kou Jing-xuan, Zhao Gui-hua, Wei Qing-kuan, Xu Chao, Zhu Song, Yin Kun
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2015 Jun;27(3):285-9.
To subelone, express and identify the immune mapped protein 1 (IMP1) which encodes a surface antigen of Toxoplasma gondii.
The cDNA of T. gondii RH strain was synthesized by reverse transcription PCR, the IMP1 open reading frame (ORF) was amplified by PCR using the T. gondii RH strain cDNA as template, the PCR products were identified by TA-cloning and sequencing, then the IMPI ORF was subcloned into the Nde I and Xho I sites of the vector pET28b, and the positive recombinant pET28b-IMP1 was identified by double-digesting and sequencing. The protein of 6 x His tagged IMP1 was inducibly expressed in E. coli strain BL21 (DE3) with isopropyl β-D-1-thiogalactopyranoside (IPTG), and the induction time, concentration of IPTG and temperature gradients to optimize protein expression conditions were determined. After the cells carried IMP1 were induced by the optimized conditions and harvested, the resulting bacteria were suspended in resuspension buffer and lysed by sonication, and the supernatants were loaded onto the Ni2+ Chelating Sepharose Fast Flow column for affinity chromatography of the N-terminal 6 x His tagged IMP1 protein. Finally, the fusion IMP1 proteins were identified by Western blotting.
The ORF sequence of IMP1 was successfully subcloned from the cDNA of Toxoplasma Gondii RH strain, and the amplified product was sequenced and identified, based on which the IMP1 ORF gene was inserted into the prokaryotic expression vector pET28b, and the recombinant pET28b-IMP1 was constructed successfully. The double-digesting and sequencing results indicated the validity of the recombinant vector. And the optimized conditions for the expression of IMP1 was determined, namely 0.3 mmol/L IPTG induction for 9 h at 20 °C. Furthermore, IMP1 protein was expressed solubly and chelated on Ni2 sepharose beads with high affinity, thus this protein could be purified efficiently by affinity chromatography. The pure fusion protein was confirmed with fine immunocompetence by SDS-PAGE and Western blotting.
IMP1 protein can be high efficiently expressed by the E. coli prokaryotic expression systems, the protein of IMP1 is soluble and has stable characters. The study may lay a useful foundation for the following works including in vivo expression of IMP1, crystal structure study of IMP1 and anti-toxoplasmosis subunit vaccine development.
克隆、表达并鉴定编码刚地弓形虫一种表面抗原的免疫定位蛋白1(IMP1)。
通过逆转录PCR合成刚地弓形虫RH株的cDNA,以刚地弓形虫RH株cDNA为模板,通过PCR扩增IMP1开放阅读框(ORF),PCR产物经TA克隆和测序鉴定,然后将IMP1 ORF亚克隆到载体pET28b的Nde I和Xho I位点,通过双酶切和测序鉴定阳性重组体pET28b-IMP1。用异丙基-β-D-1-硫代半乳糖苷(IPTG)在大肠杆菌BL21(DE3)菌株中诱导表达6×His标签的IMP1蛋白,确定诱导时间、IPTG浓度和温度梯度以优化蛋白表达条件。在优化条件下诱导携带IMP1的细胞并收获后,将所得细菌悬浮于重悬缓冲液中,通过超声裂解,将上清液加载到Ni2+螯合琼脂糖快速流动柱上,对N端6×His标签的IMP1蛋白进行亲和层析。最后,通过蛋白质印迹法鉴定融合IMP1蛋白。
成功从刚地弓形虫RH株cDNA中克隆出IMP1的ORF序列,对扩增产物进行测序和鉴定,在此基础上,将IMP1 ORF基因插入原核表达载体pET28b,成功构建重组体pET28b-IMP1。双酶切和测序结果表明重组载体有效。确定了IMP1表达的优化条件,即在20℃下用0.3 mmol/L IPTG诱导9 h。此外,IMP1蛋白以可溶形式表达,并与Ni2琼脂糖珠具有高亲和力螯合,因此该蛋白可通过亲和层析高效纯化。通过SDS-PAGE和蛋白质印迹法证实纯融合蛋白具有良好的免疫活性。
IMP1蛋白可通过大肠杆菌原核表达系统高效表达,IMP1蛋白可溶且性质稳定。该研究可为IMP1的体内表达、IMP1晶体结构研究及抗弓形虫亚单位疫苗研发等后续工作奠定有益基础。