Molecular basis for arginine C-terminal degron recognition by Cul2FEM1 E3 ligase.
Nat Chem Biol
; 17(3): 254-262, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33398168
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Arginina
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Proteínas de Transporte
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Proteínas de Ciclo Celular
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Complexos Ubiquitina-Proteína Ligase
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Complexo de Endopeptidases do Proteassoma
Limite:
Humans
Idioma:
En
Revista:
Nat Chem Biol
Assunto da revista:
BIOLOGIA
/
QUIMICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China