Systemwide disassembly and assembly of SCF ubiquitin ligase complexes

Baek, Kheewoong; Scott, Daniel C.; Henneberg, Lukas T.; King, Moeko T.; Mann, Matthias; Schulman, Brenda A.

doi:10.1016/j.cell.2023.04.036

Cited by 4 publications

(2 citation statements)

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“…Component availability and exchange rates, both spontaneous and catalyzed, are widely used strategies in the regulation of CRL1 networks (46), and we expect these effects to be at work in CRL3 KCTD networks as well.…”

Section: Discussionmentioning

confidence: 93%

“…S10), which consists of residues F69-R94 in KCTD5. These elements contact H2, H4 and H5 in the cullin-repeat 1 (CR1) domain of their cognate cullins and include residues that are displaced by CAND1 to promote SR exchange (46,47). In the dimeric KLHL and SPOP BTB families, the v-loop includes the critical φ-X-E motif (4,48), but this motif is not found in the v-loops of the KCTD family (6), even though members of both families bind to CUL3 with nanomolar affinity.…”

Section: Kctd5 Btb /Cul3 Subcomplexmentioning

confidence: 99%

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Structure and dynamics of a pentameric KCTD5/Cullin3/Gβγ E3 ubiquitin ligase complex

Nguyen,

Rath,

Devost

et al. 2023

Preprint

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Heterotrimeric G proteins can be regulated by post-translational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C-terminal domain (CTD), engages CUL3 to form the central scaffold of a cullin-RING E3 ligase complex (CRL3KCTD5) that ubiquitylates Gβγ and reduces Gβγ protein levels in cells. The cryo-EM structure of a 5:5:5 KCTD5/CUL3NTD/Gβ1γ2 assembly reveals a highly dynamic complex with rotations of over 60° between the KCTD5BTB/CUL3NTD and KCTD5CTD/Gβγ moieties of the structure. CRL3KCTD5 engages the E3 ligase ARIH1 to ubiquitylate Gβγ in an E3-E3 super-assembly, and extension of the structure to include full-length CUL3 with RBX1 and an ARIH1~ubiquitin conjugate reveals that some conformational states position the ARIH1~ubiquitin thioester bond to within 10 Å of lysine-23 of Gβ and likely represent priming complexes. Most previously described CRL/substrate structures have consisted of monovalent complexes and have involved flexible peptide substrates. The structure of the KCTD5/CUL3NTD/Gβγ complex shows that the oligomerization of a substrate receptor can generate a polyvalent E3 ligase complex and that the internal dynamics of the substrate receptor can position a structured target for ubiquitylation in a CRL3 complex.

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Section: Discussionmentioning

confidence: 93%