Targeting the ATG5-ATG16L1 Protein-Protein Interaction with a Hydrocarbon-Stapled Peptide Derived from ATG16L1 for Autophagy Inhibition
Targeting the ATG5-ATG16L1 Protein-Protein Interaction with a Hydrocarbon-Stapled Peptide Derived from ATG16L1 for Autophagy Inhibition
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DOI：
10.1021/jacs.2c07648
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发表时间：
2022-09-15
影响因子：
15
通讯作者：
Watanabe, Takumi
中科院分区：
文献类型：
--
作者：
Cui, Jin;Ogasawara, Yuta;Watanabe, Takumi
自噬的选择性调节是一种有前途的治疗策略，特别是对于癌症治疗。然而，缺乏特异性自噬抑制剂限制了这一策略。ATG 12的形成？ATG 5？ATG 16 L1复合物对于靶向ATG 12？ATG 5与适当的膜结合并产生LC 3-II用于自噬的进展。因此，针对ATG 5？ATG 16 L1蛋白？蛋白质相互作用（PPIs）可能以高度特异性抑制早期自噬。在本文中，我们报道了一种来源于ATG 16 L1的钉合肽，该肽对ATG 5具有强的结合亲和力，对蛋白水解具有显著的抗性，并且在细胞中具有显著的自噬抑制活性。
Selective modulation of autophagy is a promising therapeutic strategy, especially for cancer treatment. However, the lack of specific autophagy inhibitors limits this strategy. The formation of the ATG12???ATG5???ATG16L1 complex is essential for targeting the ATG12???ATG5 conjugate to proper membranes and to generate LC3-II for the progression of autophagy. Thus, targeting ATG5???ATG16L1 protein???protein interactions (PPIs) might inhibit early stage autophagy with high specificity. In this paper, we report that a stapled peptide derived from ATG16L1 exhibits potent binding affinity to ATG5, striking resistance to proteolysis, and significant autophagy inhibition activities in cells.Superscript/Subscript Available