+
データを開く
-
基本情報
登録情報 | データベース: PDB / ID: 7xjj | ||||||
---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of the galanin-bound GALR1-miniGo complex | ||||||
![]() |
| ||||||
![]() | SIGNALING PROTEIN / GPCR / Galanin receptor 1 / miniGo | ||||||
機能・相同性 | ![]() galanin receptor binding / type 1 galanin receptor binding / type 2 galanin receptor binding / type 3 galanin receptor binding / galanin receptor activity / positive regulation of large conductance calcium-activated potassium channel activity / guanyl nucleotide binding / positive regulation of timing of catagen / positive regulation of cortisol secretion / regulation of glucocorticoid metabolic process ...galanin receptor binding / type 1 galanin receptor binding / type 2 galanin receptor binding / type 3 galanin receptor binding / galanin receptor activity / positive regulation of large conductance calcium-activated potassium channel activity / guanyl nucleotide binding / positive regulation of timing of catagen / positive regulation of cortisol secretion / regulation of glucocorticoid metabolic process / negative regulation of lymphocyte proliferation / negative regulation of adenylate cyclase activity / neuropeptide hormone activity / neuropeptide binding / G protein-coupled peptide receptor activity / feeding behavior / vesicle docking involved in exocytosis / insulin secretion / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / peptide hormone binding / response to immobilization stress / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / neuropeptide signaling pathway / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / protein kinase A signaling / Peptide ligand-binding receptors / cAMP-mediated signaling / secretory granule / locomotory behavior / muscle contraction / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / response to insulin / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / response to estrogen / 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 / cell body / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / response to xenobiotic stimulus / positive regulation of apoptotic process / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / neuronal cell body / synapse / dendrite / protein-containing complex binding / GTP binding / signal transduction 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: 3.3 Å | ||||||
![]() | Jiang, W. / Zheng, S. | ||||||
資金援助 | ![]()
| ||||||
![]() | ![]() タイトル: Structural insights into galanin receptor signaling. 著者: Wentong Jiang / Sanduo Zheng / ![]() 要旨: Galanin is a biologically active neuropeptide, and functions through three distinct G protein–coupled receptors (GPCRs), namely GALR1, GALR2, and GALR3. GALR signaling plays important roles in ...Galanin is a biologically active neuropeptide, and functions through three distinct G protein–coupled receptors (GPCRs), namely GALR1, GALR2, and GALR3. GALR signaling plays important roles in regulating various physiological processes such as energy metabolism, neuropathic pain, epileptic activity, and sleep homeostasis. GALR1 and GALR3 signal through the Gi/o pathway, whereas GALR2 signals mainly through the Gq/11 pathway. However, the molecular basis for galanin recognition and G protein selectivity of GALRs remains poorly understood. Here, we report the cryoelectron microscopy structures of the GALR1-Go and the GALR2-Gq complexes bound to the endogenous ligand galanin or spexin. The galanin peptide mainly adopts an alpha helical structure, which binds at the extracellular vestibule of the receptors, nearly parallel to the membrane plane without penetrating deeply into the receptor core. Structural analysis combined with functional studies reveals important structural determinants for the G protein selectivity of GALRs as well as other class A GPCRs. In addition, we show that the zinc ion is a negative allosteric regulator of GALR1 but not GALR2. Our studies provide insight into the mechanisms of G protein selectivity of GPCRs and highlight a potential function of the neuromodulator zinc ion as a modulator of GPCR signaling in the central nervous system. | ||||||
履歴 |
|
-
構造の表示
構造ビューア | 分子: ![]() ![]() |
---|
-
ダウンロードとリンク
-
ダウンロード
PDBx/mmCIF形式 | ![]() | 210.7 KB | 表示 | ![]() |
---|---|---|---|---|
PDB形式 | ![]() | 162.1 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.1 MB | 表示 | ![]() |
---|---|---|---|---|
文書・詳細版 | ![]() | 1.1 MB | 表示 | |
XML形式データ | ![]() | 41 KB | 表示 | |
CIF形式データ | ![]() | 60.9 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 | ![]() 33229MC ![]() 7xjkC ![]() 7xjlC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
---|---|
類似構造データ | 類似検索 - 機能・相同性 ![]() |
-
リンク
-
集合体
登録構造単位 | ![]()
|
---|---|
1 |
|
-
要素
-タンパク質 , 2種, 2分子 AE
#1: タンパク質 | 分子量: 25447.115 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 参照: UniProt: A0A1W2PRJ7, UniProt: A0A1W2PP38, UniProt: P09471 |
---|---|
#4: タンパク質 | 分子量: 38382.930 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
-Guanine nucleotide-binding protein ... , 2種, 2分子 BG
#2: タンパク質 | 分子量: 37416.930 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P62873 |
---|---|
#5: タンパク質 | 分子量: 7845.078 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P59768 |
-タンパク質・ペプチド / 抗体 , 2種, 2分子 CS
#3: タンパク質・ペプチド | 分子量: 3161.446 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) ![]() |
---|---|
#6: 抗体 | 分子量: 31857.369 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
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 |
-
試料調製
構成要素 | 名称: Galanin-bound Galanin receptor type 1 in complex with miniGalphao, Gbeta/gamma subunit and a single-chain variable fragment (scFv16) タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
分子量 | 実験値: NO | ||||||||||||||||||||
由来(天然) | 生物種: ![]() | ||||||||||||||||||||
由来(組換発現) | 生物種: ![]() | ||||||||||||||||||||
緩衝液 | pH: 7.4 | ||||||||||||||||||||
緩衝液成分 |
| ||||||||||||||||||||
試料 | 濃度: 5.1 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 | ||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 281.15 K |
-
電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS |
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): 2200 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-
解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19_4092: / 分類: 精密化 | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EMソフトウェア | 名称: ![]() | ||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 426045 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: RIGID BODY FIT | ||||||||||||||||||||||||
拘束条件 |
|