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-Structure paper
タイトル | Structural basis for the ubiquitination of G protein βγ subunits by KCTD5/Cullin3 E3 ligase. |
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ジャーナル・号・ページ | Sci Adv, Vol. 9, Issue 28, Page eadg8369, Year 2023 |
掲載日 | 2023年7月14日 |
著者 | Wentong Jiang / Wei Wang / Yinfei Kong / Sanduo Zheng / |
PubMed 要旨 | 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)- ...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. |
リンク | Sci Adv / PubMed:37450587 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.8 - 3.27 Å |
構造データ | EMDB-35212, PDB-8i79: EMDB-36367, PDB-8jkb: |
由来 |
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キーワード | SIGNALING PROTEIN / CUL3 / ubiquitination / E3 ligase / PROTEIN BINDING / GPCR signaling |