过敏性疾病作为全球范围内影响最为广泛的疾病之一，相关分子机理研究和新型抗过敏药物研发是社会发展中迫切需要解决的关键问题。肥大细胞激活过程是过敏反应中， “过敏抗原识别-过敏效应发生”的关键效应环节。该过程的分子发生机制是发现新型抗过敏药物的理论基础。肥大细胞激活过程中，小分子Ap4A，通过快速，剧烈的浓度变化响应过敏原刺激，释放肥大细胞的标志转录因子MITF，促进过敏反应发生。然而，相关的分子机制目前还没有报道。在本项目中，我们将结合结构生物学，化学生物学和细胞生物学的多种研究方法，深入理解Ap4A利用特异的磷酯链长度结合调节蛋白（HINT1），破坏HINT1和肥大细胞标志转录因子MITF的相互作用，释放MITF的转录活性的分子机制。通过此研究，深化对肥大细胞过敏激活过程的认识，并为精准设计小分子化合物干预过敏反应建立基础。

Allergic diseases are one of the most common diseases in the world. The process of mast cell activation is the key link of "antigen recognition - allergy effect" in the allergic reaction. The molecular mechanism of this process is the basis for the discovery of new anti-allergic drugs. In the process of mast cell activation, Ap4A, a small molecule, responds to allergen stimulation through rapid and drastic concentration changes, releases the mast cell marker transcription factor MITF, , and promotes allergic reaction. However, the molecular mechanisms involved have not been reported. In this project, we will combine multiple research methods of structural biology, chemical biology and cell biology to deeply understand the molecular mechanism by which Ap4A with specific phospholipid chain length to bind regulatory protein (HINT1), disrupt the interaction between HINT1 and mast cell marker transcription factor MITF, and release the transcriptional activity of MITF. Through this study, we will deepen our understanding of the process of mast cell allergy activation, and establish the basis for the accurate design of small molecule compounds to intervene in allergic reactions.