Structural insights into SMCR8 C-degron recognition by FEM1B
Structural insights into SMCR8 C-degron recognition by FEM1B
复制标题
FEM1B 对 SMCR8 C-degron 识别的结构见解
DOI：
10.1016/j.bbrc.2021.04.046
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发表时间：
2021
影响因子：
3.1
通讯作者：
Xu Chao
中科院分区：
文献类型：
--
作者：
Zhao Shidong;Ru Wenwen;Chen Xinyan;Liao Shanhui;Zhu Zhongliang;Zhang Jiahai;Xu Chao
C-degrons在靶向Cullin-RING E3连接酶复合物的受体蛋白以启动蛋白质降解方面发挥关键作用。FEM1蛋白，包括FEM1A、FEM1B和FEM1C，作为受体特异性识别Arg/ c -degron，从而实现crl2介导的蛋白周转。除了CDK5R1外，很少有底物被鉴定为FEM1B。我们发现crl2fem1b也能识别SMCR8异构体的C-degron，并通过展示FEM1B与SMCR8结合的结构揭示了FEM1B对SMCR8的识别。我们的工作提供了CRL2FEM1Bin调节SMCR8寿命的作用，SMCR8是一种关键的自噬调节剂。
C-degrons play critical roles in targeting the receptor proteins of Cullin-RING E3 ligase complexes to initiate protein degradation. FEM1 proteins, including FEM1A, FEM1B, and FEM1C, act as the receptors to specifically recognize Arg/C-degrons to enable CRL2-mediated protein turnover. Very few substrates have been identified for FEM1B, except CDK5R1. We found that CRL2FEM1Balso recognizes the C-degron of an SMCR8 isoform, and uncovered the recognition of SMCR8 by FEM1B through presenting the structure of FEM1B bound to SMCR8. Our work provides insights into the role of CRL2FEM1Bin regulating the lifetime of SMCR8, a critical autophagy regulator.