结核分枝杆菌编码大量的毒素-抗毒素系统（TA），提示了其参与了结核分枝杆菌的发病机理、药物耐受以及潜伏感染。我们在前期研究中，对结核分枝杆菌一对推测为IV型的TA系统Rv1045-1044深入研究发现，Rv1045和Rv1044组成一对典型的TA。毒蛋白的结构解析表明，其编码鸟苷酰转移酶样蛋白，提示毒蛋白的毒性发挥依赖于转移GMP到靶分子（蛋白或者核酸）引发毒性，但是具体机制不明；Co-IP研究表明，Rv1045和Rv1044存在相互作用，与之前推测的IV型TA毒蛋白-抗毒蛋白无相互作用相悖，提示抗毒蛋白Rv1044通过相互作用发挥抗毒机制。为深入研究毒蛋白Rv1045的作用靶点以及抗毒蛋白Rv1044的解毒机制。我们拟通过结构生物学、生物化学、细菌学等技术手段，明确毒蛋白Rv1045的毒性机制以及抗毒蛋白Rv1044的解毒机制。预期结果将为结核分枝杆菌的潜伏感染机制提供理论依据。

M. tuberculosis (Mtb) encodes an exceptionally large number of toxin-antitoxin (TA) systems, hinting their involvement in pathogenesis , drug resistance and latent infection. In the previous study, we choosed one TA pair named Rv1045-1044, which was predicted to be IV type TA . and found that the expression of Rv1045 inhibited the growth of E.coli, suggesting toxicity of Rv1045.when the expression of both Rv1045 and Rv1044 was induced, toxicity of Rv1045 was neutralized, implying Rv1044 counteracted the growth inhibition caused by Rv1045. Structural analysis of the Rv1045 indicated that it encodes a guanylyltransferase-like protein, suggesting that the toxicity of the Rv1045 depends on the transfer of GMP to the target molecule (protein or nucleic acid), but the specific mechanism is unknown. The Co-IP experiment demonstrated that Rv1045 and Rv1044 interact directly with each other. This behavior is atypical for type IV TA family members. Suggesting toxicity neutralization was caused by Rv1045 and Rv1044 physical interaction. To further understand the toxicity mechanism of Rv1045 and antitoxicity mechanism of Rv1044. We intend to clarify the toxicity mechanism of the Rv1045 and the detoxification mechanism of the Rv1044 combining with structural biology, biochemistry, and bacteriology. Our project will provide a theoretical basis for the latent infection mechanism of M. tuberculosis.