8U81

KCTD5/Cullin3/Gbeta1gamma2 Complex: State A From Composite RELION Multi-body Refinement Map

This is a non-PDB format compatible entry.

Summary for 8U81

• Entry DOI: 10.2210/pdb8u81/pdb
• EMDB information: 41996
• Descriptor: BTB/POZ domain-containing protein KCTD5, Cullin-3, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (4 entities in total)
• Functional Keywords: cullin family protein, proteasome-mediated ubiquitin-dependent protein catabolic process, complex, ubiquitin-dependent protein catabolic process, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 20
• Total formula weight: 578957.64

Authors

Kuntz, D.A.,Nguyen, D.M.,Narayanan, N.,Prive, G.G. (deposition date: 2023-09-15, release date: 2023-10-11, Last modification date: 2024-05-01)

Primary citation

Nguyen, D.M.,Rath, D.H.,Devost, D.,Petrin, D.,Rizk, R.,Ji, A.X.,Narayanan, N.,Yong, D.,Zhai, A.,Kuntz, D.A.,Mian, M.U.Q.,Pomroy, N.C.,Keszei, A.F.A.,Benlekbir, S.,Mazhab-Jafari, M.T.,Rubinstein, J.L.,Hebert, T.E.,Prive, G.G.
Structure and dynamics of a pentameric KCTD5/CUL3/G beta gamma E3 ubiquitin ligase complex.
Proc.Natl.Acad.Sci.USA, 121:e2315018121-e2315018121, 2024

PubMed 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) that ubiquitylates Gβγ and reduces Gβγ protein levels in cells. The cryo-EM structure of a 5:5:5 KCTD5/CUL3/Gβγ assembly reveals a highly dynamic complex with rotations of over 60° between the KCTD5/CUL3 and KCTD5/Gβγ moieties of the structure. CRL3 engages the E3 ligase ARIH1 to ubiquitylate Gβγ in an E3-E3 superassembly, 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/CUL3/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.

PubMed: 38625940
DOI: 10.1073/pnas.2315018121

Experimental method

ELECTRON MICROSCOPY (3.82 Å)