细胞自噬是真核细胞所特有的对细胞内受损细胞器及长寿命蛋白通过溶酶体途径进行降解的细胞生物学过程。自噬异常调节会导致一系列的疾病，例如衰老、癌症和神经退行性疾病等。自噬相关蛋白Atg4B通过介导的proLC3至LC3-I的转化以及LC3-PE的去脂基化，调控整个自噬的进程，但Atg4B识别和酶切LC3-PE分子机制目前还不清楚。本项目拟利用化学合成的脂基化蛋白LC3-PE作为工具，研究Atg4B对底物proLC3和LC3-PE酶切效率的差异，探究脂肪酸链及其膜存在的条件下Atg4B酶切活性的变化，验证Atg4B存在特异性识别脂基化蛋白LC3-PE的结构域，及Atg4B是如何利用其独特的结构域调控LC3-PE的去脂基化。项目预期将揭示Atg4B识别和酶切LC3-PE的分子机制，建立Atg4B酶活性的调控模型，项目研究成果将拓展我们对自噬分子机理的认识，为开发新型Atg4B抑制剂提供科学依据。

Autophagy is a cell-based biological process that is unique to eukaryotic cells and that degrades intracellularly damaged organelles and long-lived proteins by the lysosomal pathway. Abnormal regulation of autophagy leads to a range of diseases, such as aging, cancer and neurodegenerative diseases. Atg4B regulates the process of autophagy by mediating the transformation of proLC3 to LC3-I and delipidation of LC3-PE. However, the molecular mechanism of LC3-PE delipidation by Atg4B is unclear. In the present study, the catalytic efficiency of Atg4B for proLC3 and LC3-PE will be tested using chemically synthesized lipidated protein LC3-PE as a tool; the effect of the fatty acid chain and membrane on Atg4B recognition also will be explored; It will be verified that Atg4B has LC3-PE association region and the how Atg4 utilizes its unique region to regulate the delipidation of LC3-PE. The present study is expected to reveal the molecular mechanism of Atg4B recognition and cleavage of LC3-PE, and to establish a working model of Atg4B. The results will help us to better understand the molecular mechanism of autophagy, and it has implications in providing a scientific basis for the development of new Atg4 inhibitors.