Molecular basis for ubiquitin ligase CRL2FEM1C-mediated recognition of C-degron.

Proteome integrity depends on the ubiquitin-proteasome system to degrade unwanted or abnormal proteins. In addition to the N-degrons, C-terminal residues of proteins can also serve as degradation signals (C-degrons) that are recognized by specific cullin-RING ubiquitin ligases (CRLs) for proteasomal degradation. FEM1C is a CRL2 substrate receptor that targets the ...
C-terminal arginine degron (Arg/C-degron), but the molecular mechanism of substrate recognition remains largely elusive. Here, we present crystal structures of FEM1C in complex with Arg/C-degron and show that FEM1C utilizes a semi-open binding pocket to capture the C-terminal arginine and that the extreme C-terminal arginine is the major structural determinant in recognition by FEM1C. Together with biochemical and mutagenesis studies, we provide a framework for understanding molecular recognition of the Arg/C-degron by the FEM family of proteins.
Mesh Terms:
Amino Acid Sequence, Arginine, Binding Sites, Carrier Proteins, Cell Cycle Proteins, Cloning, Molecular, Crystallography, X-Ray, Escherichia coli, Gene Expression, Genetic Vectors, HEK293 Cells, Humans, Models, Molecular, Proteasome Endopeptidase Complex, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Proteolysis, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Substrate Specificity, Ubiquitin-Protein Ligase Complexes
Nat Chem Biol
Date: Dec. 01, 2020
Download Curated Data For This Publication
231878
Switch View:
  • Interactions 8