a Department of Pharmacology , University of Colorado School of Medicine , Aurora , CO , USA.
b Protein Metabolism Medical Research Center and Department of Biomedical Sciences, College of Medicine , Seoul National University , Seoul , Republic of Korea.
Autophagy. 2019 Apr;15(4):735-737. doi: 10.1080/15548627.2019.1569935. Epub 2019 Jan 22.
SQSTM1/p62 facilitates responses to various cellular stresses and has been implicated in human diseases. This protein functions as a major cytoplasmic signaling hub and has multiple binding partners, including arginylated (Nt-R) proteins that are recognized by the ZZ domain of SQSTM1/p62 (SQSTM1/p62). We have determined the molecular mechanism of Nt-R recognition using a combination of biochemical and NMR approaches and obtained the crystal structure of SQSTM1/p62 in complex with Nt-R. We found that binding of SQSTM1/p62 to Nt-R induces SQSTM1/p62 puncta formation and macroautophagy/autophagy and identified a regulatory linker (RL) region of SQSTM1/p62 that associates with SQSTM1/p62 in vitro. Our findings suggest a mechanism for SQSTM1/p62 autoregulation that can be essential in mediating autophagy.
SQSTM1/p62 促进对各种细胞应激的反应，并与人类疾病有关。该蛋白作为主要的细胞质信号枢纽发挥作用，具有多个结合伴侣，包括被 SQSTM1/p62（SQSTM1/p62）的 ZZ 结构域识别的精氨酸化（Nt-R）蛋白。我们使用生化和 NMR 方法的组合确定了 Nt-R 识别的分子机制，并获得了 SQSTM1/p62 与 Nt-R 复合物的晶体结构。我们发现 SQSTM1/p62 与 Nt-R 的结合诱导 SQSTM1/p62 斑点形成和巨自噬/自噬，并鉴定了 SQSTM1/p62 的一个调节连接（RL）区域，该区域在体外与 SQSTM1/p62 相关联。我们的发现为 SQSTM1/p62 自身调控提供了一种机制，这对于介导自噬可能是至关重要的。
