MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China.
MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China.
Biochem Biophys Res Commun. 2021 Jun 11;557:236-239. doi: 10.1016/j.bbrc.2021.04.046. Epub 2021 Apr 20.
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 CRL2 also 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 CRL2 in regulating the lifetime of SMCR8, a critical autophagy regulator.
C-degrons 在靶向 Cullin-RING E3 连接酶复合物的受体蛋白以启动蛋白降解中发挥关键作用。FEM1 蛋白（包括 FEM1A、FEM1B 和 FEM1C）作为受体，特异性识别 Arg/C-degrons，以实现 CRL2 介导的蛋白质周转。除了 CDK5R1 之外，很少有底物被鉴定为 FEM1B 的底物。我们发现 CRL2 还识别 SMCR8 同工型的 C-degron，并通过展示与 SMCR8 结合的 FEM1B 结构揭示了 FEM1B 对 SMCR8 的识别。我们的工作深入了解了 CRL2 在调节关键自噬调节剂 SMCR8 的寿命中的作用。
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