本项目建立在我们针刺治疗哮喘临床有效，并经多年针刺抗哮喘作用机制和效应物质基础研究有所发现的基础之上。我们的前期研究证明Transgelin-2(TG2)作为针刺抗哮喘靶标，在调节气道平滑肌细胞收缩舒张功能中具有关键作用。然而由于缺少TG2全长结构、跨膜段长度与方向等信息，TG2介导的针刺舒张气道平滑肌跨膜信号传导机制尚不清楚。我们的预初实验初步克隆了经质谱验证的包含全部220个氨基酸的全长TG2蛋白，并采用座滴法初步获得TG2蛋白微晶，利用结构生物学分析预测了TG2蛋白跨膜段。本项目拟在上述工作基础上，应用结构生物学、分子生物学等技术，进一步明确针刺抗哮喘靶标TG2的全长晶体结构与跨膜结构域，阐明TG2在针刺舒张气道平滑肌过程中的跨膜结构与生物学信号传导机制。以期为基于针灸效应物质基础的针刺抗哮喘作用机制研究和创新药物发展提供一条可能的新途径。

The project is based on our clinical efficacy of acupuncture treatment for patients with asthma and years of mechanism study. Our previous studies showed that transgelin-2 (TG2) plays a key role in the regulation of airway smooth muscle as the target for acupuncture anti-asthmatic effects. However, the signal transmembrane transduction mechanism of relaxing airway smooth muscle by acupuncture is still unclear due to the lack of information such as the full-length crystal structure of TG2, the length and direction of the transmembrane segment. Our preliminary studies have cloned full-length TG2 protein containing all 220 amino acids, and the full-length sequence matching has been verified by mass spectrometry. TG2 protein crystals were preliminarily obtained using the method entitled “Sitting Drop”. The transmembrane segment of human TG2 protein has been predicted by structural biology algorithm. On the basis of these studies, the project intends to analyze full-length TG2 crystal structure and transmembrane domain of TG2, and further illuminate the transmembrane structure and biological signal transduction mechanism of TG2 in the process of relaxing airway smooth muscle by acupuncture through the application of structural biology, molecular biology and other technologies. Our study will clarify the mechanism of anti-asthmatic effects of acupuncture and the related material basis, and provides a new pipeline for target discovery and innovative drug development based on acupuncture research.