Structural insights into SMCR8 C-degron recognition by FEM1B

Biochem Biophys Res Commun. 2021 Jun 11:557:236-239. doi: 10.1016/j.bbrc.2021.04.046. Epub 2021 Apr 20.

Abstract

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 CRL2FEM1B 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 CRL2FEM1B in regulating the lifetime of SMCR8, a critical autophagy regulator.

Keywords: Cullin-RING E3 ligase; Degron; Protein degradation; Ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Crystallography, X-Ray
  • Gene Expression
  • Proteolysis
  • Ubiquitin-Protein Ligases / chemistry*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • FEM1B protein, human
  • SMCR8 protein, human
  • CULL-RING ligase, human
  • Ubiquitin-Protein Ligases