Mechanism of Ψ-Pro/C-degron recognition by the CRL2^FEM1B ubiquitin ligase.

ABSTRACT: The E3 ligase-degron interaction determines the specificity of the ubiquitin‒proteasome system. We recently discovered that FEM1B, a substrate receptor of Cullin 2-RING ligase (CRL2), recognizes C-degrons containing a C-terminal proline. By solving several cryo-EM structures of CRL2^FEM1B bound to different C-degrons, we elucidate the dimeric assembly of the complex. Furthermore, we reveal distinct dimerization states of unmodified and neddylated CRL2^FEM1B to uncover the NEDD8-mediated activation mechanism of CRL2^FEM1B. Our research also indicates that, FEM1B utilizes a bipartite mechanism to recognize both the C-terminal proline and an upstream aromatic residue within the substrate. These structural findings, complemented by in vitro ubiquitination and in v

SUBMITTER: Chen X 

PROVIDER: S-EPMC11053023 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature