During autophagy the enzyme Atg3 catalyzes the covalent conjugation of LC3 to the amino group of phosphatidylethanolamine (PE) lipids, which is one of the key steps in autophagosome formation. Here, we have demonstrated that an N-terminal conserved region of human Atg3 (hAtg3) communicates information from the N-terminal membrane curvature-sensitive amphipathic helix (AH), which presumably targets the enzyme to the tip of phagophore, to the C-terminally located catalytic core for LC3–PE conjugation. Mutations in the putative communication region greatly reduce or abolish the ability of hAtg3 to catalyze this conjugation in vitro and in vivo, and alter the membrane-bound conformation of the wild-type protein, as reported by NMR. Collectively, our results demonstrate that the N-terminal conserved region of hAtg3 works in concert with its geometry-selective AH to promote LC3–PE conjugation only on the target membrane, and substantiate the concept that highly curved membranes drive spatial regulation of the autophagosome biogenesis during autophagy.

在自噬过程中，Atg3 酶催化 LC3 与磷脂酰乙醇胺 (PE) 脂质的氨基共价结合，这是自噬体形成的关键步骤之一。在这里，我们已经证明，人类 Atg3 (hAtg3) 的 N 端保守区域将来自 N 端膜曲率敏感两亲螺旋 (AH) 的信息传递给 C- LC3-PE结合的末端催化核心。如核磁共振所报道，假定的通讯区域中的突变大大降低或消除了 hAtg3 在体外和体内催化这种结合的能力，并改变了野生型蛋白质的膜结合构象。总的来说，