Recognition of the CCT5 di-Glu degron by CRL4^DCAF12 is dependent on TRiC assembly.

ABSTRACT: Assembly Quality Control (AQC) E3 ubiquitin ligases target incomplete or incorrectly assembled protein complexes for degradation. The CUL4-RBX1-DDB1-DCAF12 (CRL4^DCAF12 ) E3 ligase preferentially ubiquitinates proteins that carry a C-terminal double glutamate (di-Glu) motif. Reported CRL4^DCAF12 di-Glu-containing substrates include CCT5, a subunit of the TRiC chaperonin. How DCAF12 engages its substrates and the functional relationship between CRL4^DCAF12 and CCT5/TRiC is currently unknown. Here, we present the cryo-EM structure of the DDB1-DCAF12-CCT5 complex at 2.8 Å resolution. DCAF12 serves as a canonical WD40 DCAF substrate receptor and uses a positively charged pocket at the center of the β-propeller to bind the C-terminus of CCT5. DCAF12 specifically re

SUBMITTER: Pla-Prats C 

PROVIDER: S-EPMC9929631 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature