Molecular basis for C-degron recognition by CRL2^APPBP2 ubiquitin ligase.

ABSTRACT: E3 ubiquitin ligases determine the specificity of eukaryotic protein degradation by selective binding to destabilizing protein motifs, termed degrons, in substrates for ubiquitin-mediated proteolysis. The exposed C-terminal residues of proteins can act as C-degrons that are recognized by distinct substrate receptors (SRs) as part of dedicated cullin-RING E3 ubiquitin ligase (CRL) complexes. APPBP2, an SR of Cullin 2-RING ligase (CRL2), has been shown to recognize R-x-x-G/C-degron; however, the molecular mechanism of recognition remains elusive. By solving several cryogenic electron microscopy structures of active CRL2^APPBP2 bound with different R-x-x-G/C-degrons, we unveiled the molecular mechanisms underlying the assembly of the CRL2^APPBP2 dimer and tetramer, as well

SUBMITTER: Zhao S 

PROVIDER: S-EPMC10614623 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature