Orphan quality control by an SCF ubiquitin ligase directed to pervasive C-degrons.
Nat Commun
; 14(1): 8363, 2023 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-38102142
ABSTRACT
Selective protein degradation typically involves substrate recognition via short linear motifs known as degrons. Various degrons can be found at protein termini from bacteria to mammals. While N-degrons have been extensively studied, our understanding of C-degrons is still limited. Towards a comprehensive understanding of eukaryotic C-degron pathways, here we perform an unbiased survey of C-degrons in budding yeast. We identify over 5000 potential C-degrons by stability profiling of random peptide libraries and of the yeast Cterminome. Combining machine learning, high-throughput mutagenesis and genetic screens reveals that the SCF ubiquitin ligase targets ~40% of degrons using a single F-box substrate receptor Das1. Although sequence-specific, Das1 is highly promiscuous, recognizing a variety of C-degron motifs. By screening for full-length substrates, we implicate SCFDas1 in degradation of orphan protein complex subunits. Altogether, this work highlights the variety of C-degron pathways in eukaryotes and uncovers how an SCF/C-degron pathway of broad specificity contributes to proteostasis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Ligases SKP Culina F-Box
/
Degrons
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article