Dataset Information


Recognition of the Diglycine C-End Degron by CRL2KLHDC2 Ubiquitin Ligase.

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.

PROVIDER: S-EPMC6294321 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC6003881 | BioStudies
| S-EPMC6145449 | BioStudies
| S-EPMC9281121 | BioStudies
| S-EPMC4729826 | BioStudies
| S-EPMC3812159 | BioStudies
| S-EPMC6628059 | BioStudies
| S-EPMC7458402 | BioStudies
| S-EPMC3189519 | BioStudies
| S-EPMC3003441 | BioStudies
| S-EPMC8045714 | BioStudies