Recognition of the Diglycine C-End Degron by CRL2KLHDC2 Ubiquitin Ligase.
Mol Cell
; 72(5): 813-822.e4, 2018 12 06.
Article
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Selenoproteins
/
Ubiquitin-Specific Proteases
/
Glycylglycine
/
Antigens, Neoplasm
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2018
Document type:
Article
Affiliation country:
United States