Structure and dynamics of a pentameric KCTD5/CUL3/Gβγ E3 ubiquitin ligase complex.

ABSTRACT: Heterotrimeric G proteins can be regulated by posttranslational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C-terminal domain, engages CUL3 to form the central scaffold of a cullin-RING E3 ligase complex (CRL3^KCTD5) that ubiquitylates Gβγ and reduces Gβγ protein levels in cells. The cryo-EM structure of a 5:5:5 KCTD5/CUL3^NTD/Gβ₁γ₂ assembly reveals a highly dynamic complex with rotations of over 60° between the KCTD5^BTB/CUL3^NTD and KCTD5^CTD/Gβγ moieties of the structure. CRL3^KCTD5 engages the E3 ligase ARIH1 to ubiquitylate Gβγ in an E3-E3 superassembly, and extension of the structure to include full-length CUL3 with

SUBMITTER: Nguyen DM 

PROVIDER: S-EPMC11047111 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature