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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Cryo-EM structure of KCTD5 in complex with Gbeta gamma subunits | |||||||||
![]() | EM density map of KCTD5_Gng2/Gnb1 complex | |||||||||
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![]() | ubiquitination / GPCR signaling / PROTEIN BINDING | |||||||||
機能・相同性 | ![]() Cul3-RING ubiquitin ligase complex / cullin family protein binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / protein homooligomerization / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway ...Cul3-RING ubiquitin ligase complex / cullin family protein binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / protein homooligomerization / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / proteasome-mediated ubiquitin-dependent protein catabolic process / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / identical protein binding / membrane / nucleus / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.27 Å | |||||||||
![]() | Zheng S / Jiang W / Wang W / Kong Y | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis for the ubiquitination of G protein βγ subunits by KCTD5/Cullin3 E3 ligase. 著者: Wentong Jiang / Wei Wang / Yinfei Kong / Sanduo Zheng / ![]() 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. | |||||||||
履歴 |
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構造の表示
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マップデータ | ![]() | 80.4 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 20.6 KB 20.6 KB | 表示 表示 | ![]() |
画像 | ![]() | 58 KB | ||
Filedesc metadata | ![]() | 6.3 KB | ||
その他 | ![]() ![]() ![]() | 154 MB 151.6 MB 151.6 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 693.4 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 693 KB | 表示 | |
XML形式データ | ![]() | 14.6 KB | 表示 | |
CIF形式データ | ![]() | 17.1 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8jkbMC ![]() 8i79C M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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注釈 | EM density map of KCTD5_Gng2/Gnb1 complex | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.86 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-追加マップ: EM density map of KCTD5 Gng2/Gnb1 complex after sharpening
ファイル | emd_36367_additional_1.map | ||||||||||||
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注釈 | EM density map of KCTD5_Gng2/Gnb1 complex after sharpening | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half map of KCTD5 Gng2/Gnb1 complex
ファイル | emd_36367_half_map_1.map | ||||||||||||
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注釈 | half map of KCTD5_Gng2/Gnb1 complex | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half map of KCTD5 Gng2/Gnb1 complex
ファイル | emd_36367_half_map_2.map | ||||||||||||
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注釈 | half map of KCTD5_Gng2/Gnb1 complex | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : Cryo-EM structure of KCTD5 in complex with G protein betagamma su...
全体 | 名称: Cryo-EM structure of KCTD5 in complex with G protein betagamma subunits |
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要素 |
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-超分子 #1: Cryo-EM structure of KCTD5 in complex with G protein betagamma su...
超分子 | 名称: Cryo-EM structure of KCTD5 in complex with G protein betagamma subunits タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: ![]() ![]() |
-分子 #1: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 1 / コピー数: 5 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 41.088762 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MYPYDVPDYA YPYDVPDYAY PYDVPDYAGS GSMSELDQLR QEAEQLKNQI RDARKACADA TLSQITNNID PVGRIQMRTR RTLRGHLAK IYAMHWGTDS RLLVSASQDG KLIIWDSYTT NKVHAIPLRS SWVMTCAYAP SGNYVACGGL DNICSIYNLK T REGNVRVS ...文字列: MYPYDVPDYA YPYDVPDYAY PYDVPDYAGS GSMSELDQLR QEAEQLKNQI RDARKACADA TLSQITNNID PVGRIQMRTR RTLRGHLAK IYAMHWGTDS RLLVSASQDG KLIIWDSYTT NKVHAIPLRS SWVMTCAYAP SGNYVACGGL DNICSIYNLK T REGNVRVS RELAGHTGYL SCCRFLDDNQ IVTSSGDTTC ALWDIETGQQ TTTFTGHTGD VMSLSLAPDT RLFVSGACDA SA KLWDVRE GMCRQTFTGH ESDINAICFF PNGNAFATGS DDATCRLFDL RADQELMTYS HDNIICGITS VSFSKSGRLL LAG YDDFNC NVWDALKADR AGVLAGHDNR VSCLGVTDDG MAVATGSWDS FLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 2 / コピー数: 5 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 10.228731 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: GSALEVLFQG PGAGALEVLF QGPGSMASNN TASIAQARKL VEQLKMEANI DRIKVSKAAA DLMAYCEAHA KEDPLLTPVP ASENPFREK KFFSAIL UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #3: BTB/POZ domain-containing protein KCTD5
分子 | 名称: BTB/POZ domain-containing protein KCTD5 / タイプ: protein_or_peptide / ID: 3 / コピー数: 5 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 30.780623 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MGSSHHHHHH GSEDQVDPRL IDGKDYKDDD DKLEVLFQGP MAENHCELLP PAPSGLGAGL GGGLCRRCSA GMGALAQRPG GVSKWVRLN VGGTYFLTTR QTLCRDPKSF LYRLCQADPD LDSDKDETGA YLIDRDPTYF GPVLNYLRHG KLVINKDLAE E GVLEEAEF ...文字列: MGSSHHHHHH GSEDQVDPRL IDGKDYKDDD DKLEVLFQGP MAENHCELLP PAPSGLGAGL GGGLCRRCSA GMGALAQRPG GVSKWVRLN VGGTYFLTTR QTLCRDPKSF LYRLCQADPD LDSDKDETGA YLIDRDPTYF GPVLNYLRHG KLVINKDLAE E GVLEEAEF YNITSLIKLV KDKIRERDSR ISQMPVKHVY RVLQCQEEEL TQMVSTMSDG WKFEQLVSIG SSYNYGNEDQ AE FLCVVSK ELHNTPYGTT SEPSEKAKIL QERGSRM UniProtKB: BTB/POZ domain-containing protein KCTD5 |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 0.32 mg/mL | |||||||||
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緩衝液 | pH: 7.4 構成要素:
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グリッド | 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 40 sec. | |||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 281.15 K / 装置: FEI VITROBOT MARK IV |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 49.71 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.6 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |