ArticleScience advances2023
Structural basis for the ubiquitination of G protein βγ subunits by KCTD5/Cullin3 E3 ligase.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Pooled it
- A Global Analysis of the Complex Structural Organization of KCTD Proteins and Their Functional Implications.International journal of molecular sciences · 2026Review
- Article
- Degrons and degradation signals beyond short linear motifs.Nature chemical biology · 2026Review
- C21orf2 as a potential regulator of JAK2/STAT3 signaling in prostate cancer cell proliferation and apoptosis: an exploratory study.BMC cancer · 2026Article
- KCTD Family: Emerging Regulators of GPCR Biased Signaling.Handbook of experimental pharmacology · 2026Review
- HIV-1 vif mediates ubiquitination of the proximal protomer in the APOBEC3H dimer to induce degradation.Nature communications · 2025Article
- The G protein modifier KCTD5 tunes the decoding of neuromodulatory signals necessary for motor function in striatal neurons.PLoS biology · 2025Article
- Ubiquitination-mediated protein homeostasis in cardiovascular diseases: molecular mechanisms and therapeutic opportunities.American journal of cardiovascular disease · 2025Review
- The Cul3 ubiquitin ligase engages Insomniac as an adaptor to impact sleep and synaptic homeostasis.PLoS genetics · 2025Article
- A BTB extension and ion-binding domain contribute to the pentameric structure and TFAP2A binding of KCTD1.Structure (London, England : 1993) · 2024Article
- Emerging modes of regulation of neuromodulatory G protein-coupled receptors.Trends in neurosciences · 2024Review
- KCTD proteins regulate morphine dependence via heterologous sensitization of adenylyl cyclase 1 in mice.PLoS biology · 2024Article
- A conserved N-terminal motif of CUL3 contributes to assembly and E3 ligase activity of CRL3Nature communications · 2024Article
- KCTD Proteins Have Redundant Functions in Controlling Cellular Growth.International journal of molecular sciences · 2024Article
- Structure and dynamics of a pentameric KCTD5/CUL3/Gβγ E3 ubiquitin ligase complex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Comprehensive Analysis of the Structural Recognition between KCTD Proteins and Cullin 3.International journal of molecular sciences · 2024Article
- Neuronal-specific TNFAIP1 ablation attenuates postoperative cognitive dysfunction via targeting SNAP25 for K48-linked ubiquitination.Cell communication and signaling : CCS · 2023Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G protein-coupled receptor (GPCR) signaling is precisely controlled to avoid overstimulation that results in detrimental consequences. Gβγ signaling is negatively regulated by a Cullin3 (Cul3)-dependent E3 ligase, KCTD5, which triggers ubiquitination and degradation of free Gβγ. Here, we report the cryo-electron microscopy structures of the KCTD5-Gβγ fusion complex and the KCTD7-Cul3 complex. KCTD5 in pentameric form engages symmetrically with five copies of Gβγ through its C-terminal domain. The unique pentameric assembly of the KCTD5/Cul3 E3 ligase places the ubiquitin-conjugating enzyme (E2) and the modification sites of Gβγ in close proximity and allows simultaneous transfer of ubiquitin from E2 to five Gβγ subunits. Moreover, we show that ubiquitination of Gβγ by KCTD5 is important for fine-tuning cyclic adenosine 3´,5´-monophosphate signaling of GPCRs. Our studies provide unprecedented insights into mechanisms of substrate recognition by unusual pentameric E3 ligases and highlight the KCTD family as emerging regulators of GPCR signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.