C-terminal glutamine acts as a C-degron targeted by E3 ubiquitin ligase TRIM7.
Proc Natl Acad Sci U S A
; 119(30): e2203218119, 2022 07 26.
Article
em En
| MEDLINE
| ID: mdl-35867826
ABSTRACT
The exposed N-terminal or C-terminal residues of proteins can act, in cognate sequence contexts, as degradation signals (degrons) that are targeted by specific E3 ubiquitin ligases for proteasome-dependent degradation by N-degron or C-degron pathways. Here, we discovered a distinct C-degron pathway, termed the Gln/C-degron pathway, in which the B30.2 domain of E3 ubiquitin ligase TRIM7 (TRIM7B30.2) mediates the recognition of proteins bearing a C-terminal glutamine. By determining crystal structures of TRIM7B30.2 in complexes with various peptides, we show that TRIM7B30.2 forms a positively charged binding pocket to engage the "U"-shaped Gln/C-degron. The four C-terminal residues of a substrate play an important role in C-degron recognition, with C-terminal glutamine as the principal determinant. In vitro biochemical and cellular experiments were used to further analyze the substrate specificity and selective degradation of the Gln/C-degron by TRIM7.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ubiquitina-Proteína Ligases
/
Proteólise
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Proteínas com Motivo Tripartido
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Glutamina
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article