6LF0

Structure of FEM1C

Summary for 6LF0

• Entry DOI: 10.2210/pdb6lf0/pdb
• Descriptor: Protein fem-1 homolog C, SULFATE ION (3 entities in total)
• Functional Keywords: ubiquitination e3 ligase, protein binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 89310.62

Authors

Chen, X.,Liao, S.,Xu, C. (deposition date: 2019-11-27, release date: 2020-10-21, Last modification date: 2023-11-22)

Primary citation

Chen, X.,Liao, S.,Makaros, Y.,Guo, Q.,Zhu, Z.,Krizelman, R.,Dahan, K.,Tu, X.,Yao, X.,Koren, I.,Xu, C.
Molecular basis for arginine C-terminal degron recognition by Cul2 FEM1 E3 ligase.
Nat.Chem.Biol., 17:254-262, 2021

PubMed Abstract: Degrons are elements within protein substrates that mediate the interaction with specific degradation machineries to control proteolysis. Recently, a few classes of C-terminal degrons (C-degrons) that are recognized by dedicated cullin-RING ligases (CRLs) have been identified. Specifically, CRL2 using the related substrate adapters FEM1A/B/C was found to recognize C degrons ending with arginine (Arg/C-degron). Here, we uncover the molecular mechanism of Arg/C-degron recognition by solving a subset of structures of FEM1 proteins in complex with Arg/C-degron-bearing substrates. Our structural research, complemented by binding assays and global protein stability (GPS) analyses, demonstrates that FEM1A/C and FEM1B selectively target distinct classes of Arg/C-degrons. Overall, our study not only sheds light on the molecular mechanism underlying Arg/C-degron recognition for precise control of substrate turnover, but also provides valuable information for development of chemical probes for selectively regulating proteostasis.

PubMed: 33398168
DOI: 10.1038/s41589-020-00704-3

Experimental method

X-RAY DIFFRACTION (2.11 Å)