Recognition of the Diglycine C-End Degron by CRL2KLHDC2 Ubiquitin Ligase.
Mol Cell
; 72(5): 813-822.e4, 2018 12 06.
Article
en En
| MEDLINE
| ID: mdl-30526872
ABSTRACT
Aberrant proteins can be deleterious to cells and are cleared by the ubiquitin-proteasome system. A group of C-end degrons that are recognized by specific cullin-RING ubiquitin E3 ligases (CRLs) has recently been identified in some of these abnormal polypeptides. Here, we report three crystal structures of a CRL2 substrate receptor, KLHDC2, in complex with the diglycine-ending C-end degrons of two early-terminated selenoproteins and the N-terminal proteolytic fragment of USP1. The E3 recognizes the degron peptides in a similarly coiled conformation and cradles their C-terminal diglycine with a deep surface pocket. By hydrogen bonding with multiple backbone carbonyls of the peptides, KLHDC2 further locks in the otherwise degenerate degrons with a compact interface and unexpected high affinities. Our results reveal the structural mechanism by which KLHDC2 recognizes the simplest C-end degron and suggest a functional necessity of the E3 to tightly maintain the low abundance of its select substrates.
Palabras clave
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Banco de datos:
MEDLINE
Asunto principal:
Selenoproteínas
/
Proteasas Ubiquitina-Específicas
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Glicilglicina
/
Antígenos de Neoplasias
Idioma:
En
Año:
2018
Tipo del documento:
Article