6XKC

Crystal structure of E3 ligase

Summary for 6XKC

• Entry DOI: 10.2210/pdb6xkc/pdb
• Descriptor: Protein fem-1 homolog C (2 entities in total)
• Functional Keywords: ups, ubiquitin, e3 ligase, protein degradation, structural genomics, structural genomics consortium, sgc, ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 159747.10

Authors

Yan, X.,Dong, A.,Bountra, C.,Edwards, A.M.,Arrowsmith, C.H.,Min, J.R.,Dong, C.,Structural Genomics Consortium (SGC) (deposition date: 2020-06-26, release date: 2020-10-14, Last modification date: 2023-10-18)

Primary citation

Yan, X.,Wang, X.,Li, Y.,Zhou, M.,Li, Y.,Song, L.,Mi, W.,Min, J.,Dong, C.
Molecular basis for ubiquitin ligase CRL2 FEM1C -mediated recognition of C-degron.
Nat.Chem.Biol., 17:263-271, 2021

PubMed Abstract: 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.

PubMed: 33398170
DOI: 10.1038/s41589-020-00703-4

Experimental method

X-RAY DIFFRACTION (2.03 Å)