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基本情報
登録情報 | データベース: PDB / ID: 7x6i | ||||||
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タイトル | Cryo-EM structure of the human TRPC5 ion channel in complex with G alpha i3 subunits, class1 | ||||||
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![]() | METAL TRANSPORT / transient receptor potential | ||||||
機能・相同性 | ![]() regulation of membrane hyperpolarization / phosphatidylserine exposure on apoptotic cell surface / negative regulation of dendrite morphogenesis / Role of second messengers in netrin-1 signaling / store-operated calcium channel activity / cation channel complex / negative regulation of adenylate cyclase activity / inositol 1,4,5 trisphosphate binding / actinin binding / GTP metabolic process ...regulation of membrane hyperpolarization / phosphatidylserine exposure on apoptotic cell surface / negative regulation of dendrite morphogenesis / Role of second messengers in netrin-1 signaling / store-operated calcium channel activity / cation channel complex / negative regulation of adenylate cyclase activity / inositol 1,4,5 trisphosphate binding / actinin binding / GTP metabolic process / TRP channels / G protein-coupled dopamine receptor signaling pathway / clathrin binding / positive regulation of macroautophagy / Adenylate cyclase inhibitory pathway / positive regulation of axon extension / calcium channel complex / regulation of cytosolic calcium ion concentration / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of neuron differentiation / positive regulation of peptidyl-threonine phosphorylation / G protein-coupled receptor binding / calcium ion transmembrane transport / G-protein beta/gamma-subunit complex binding / calcium channel activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / neuron differentiation / ADP signalling through P2Y purinoceptor 12 / G alpha (z) signalling events / ADORA2B mediated anti-inflammatory cytokines production / GPER1 signaling / GDP binding / calcium ion transport / heterotrimeric G-protein complex / nervous system development / actin binding / midbody / G alpha (i) signalling events / growth cone / positive regulation of cytosolic calcium ion concentration / ATPase binding / G alpha (s) signalling events / neuron apoptotic process / Extra-nuclear estrogen signaling / cell cycle / lysosomal membrane / cell division / GTPase activity / centrosome / neuronal cell body / dendrite / positive regulation of cell population proliferation / nucleolus / GTP binding / Golgi apparatus / extracellular exosome / nucleoplasm / membrane / metal ion binding / plasma membrane / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.93 Å | ||||||
![]() | Won, J. / Jeong, H. / Lee, H.H. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Molecular architecture of the Gα-bound TRPC5 ion channel. 著者: Jongdae Won / Jinsung Kim / Hyeongseop Jeong / Jinhyeong Kim / Shasha Feng / Byeongseok Jeong / Misun Kwak / Juyeon Ko / Wonpil Im / Insuk So / Hyung Ho Lee / ![]() ![]() 要旨: G-protein coupled receptors (GPCRs) and ion channels serve as key molecular switches through which extracellular stimuli are transformed into intracellular effects, and it has long been postulated ...G-protein coupled receptors (GPCRs) and ion channels serve as key molecular switches through which extracellular stimuli are transformed into intracellular effects, and it has long been postulated that ion channels are direct effector molecules of the alpha subunit of G-proteins (Gα). However, no complete structural evidence supporting the direct interaction between Gα and ion channels is available. Here, we present the cryo-electron microscopy structures of the human transient receptor potential canonical 5 (TRPC5)-Gα complexes with a 4:4 stoichiometry in lipid nanodiscs. Remarkably, Gα binds to the ankyrin repeat edge of TRPC5 ~ 50 Å away from the cell membrane. Electrophysiological analysis shows that Gα increases the sensitivity of TRPC5 to phosphatidylinositol 4,5-bisphosphate (PIP), thereby rendering TRPC5 more easily opened in the cell membrane, where the concentration of PIP is physiologically regulated. Our results demonstrate that ion channels are one of the direct effector molecules of Gα proteins triggered by GPCR activation-providing a structural framework for unraveling the crosstalk between two major classes of transmembrane proteins: GPCRs and ion channels. | ||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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-検証レポート
文書・要旨 | ![]() | 1.6 MB | 表示 | ![]() |
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-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
-タンパク質 , 2種, 8分子 ABCDEFGH
#1: タンパク質 | 分子量: 89951.891 Da / 分子数: 4 / 由来タイプ: 組換発現 詳細: residues 766,767(SR) restriction enzyme, XbaI, residues 768-773(LEVLFQ) protease cleavage site, HRV-3C 由来: (組換発現) ![]() ![]() #2: タンパク質 | 分子量: 41399.047 Da / 分子数: 4 / Mutation: Q204L / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
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-非ポリマー , 6種, 24分子 ![](data/chem/img/PTY.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/CA.gif)
![](data/chem/img/YZY.gif)
![](data/chem/img/GTP.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/CA.gif)
![](data/chem/img/YZY.gif)
![](data/chem/img/GTP.gif)
#3: 化合物 | ChemComp-PTY / #4: 化合物 | ChemComp-Y01 / #5: 化合物 | ChemComp-ZN / #6: 化合物 | ChemComp-CA / #7: 化合物 | ChemComp-YZY / ( #8: 化合物 | ChemComp-GTP / |
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-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 |
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分子量 | 実験値: NO | ||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 8 | ||||||||||||||||||||||||
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
顕微鏡 | モデル: TFS GLACIOS |
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電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 40 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
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解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 3.93 Å / 解像度の算出法: OTHER / 粒子像の数: 18935 詳細: We combined two different maps from the same dataset (D_1300028166_em-additional-volume_P1.map.V2 and D_1300028166_em-additional-volume_P2.map.V2) to generate a composite map (D_1300028166_em- ...詳細: We combined two different maps from the same dataset (D_1300028166_em-additional-volume_P1.map.V2 and D_1300028166_em-additional-volume_P2.map.V2) to generate a composite map (D_1300028166_em-volume_P1.map.V2). The density of the G protein area could not be visualized clearly in the consensus map of this EM dataset. Therefore, we performed focused classification and local refinement to improve the density of the G protein area using symmetry expanded particles with C4 symmetry imposition, which required more number of particles. Finally, the number of particles used to reconstruct additional volume data 2 (D_1300028166_em-additional-volume_P2.map.V2) is 18,935 and the number of particles used to reconstruct additional volume data 1 (D_1300028166_em-additional-volume_P1.map.V2) is 205,343. Furthermore, the resolution stated above is based on map resolution estimates calculated by a validation tool in Phenix, FSC (model) = 0.5. 対称性のタイプ: POINT |