+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-33229 | |||||||||
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タイトル | Cryo-EM structure of the galanin-bound GALR1-miniGo complex | |||||||||
マップデータ | cryoEM map of the GALR1/Go/galanin complex | |||||||||
試料 |
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キーワード | GPCR / Galanin receptor 1 / miniGo / SIGNALING PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 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 / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / negative regulation of adenylate cyclase activity / neuropeptide hormone activity / G protein-coupled peptide receptor activity / neuropeptide binding / vesicle docking involved in exocytosis / feeding behavior / insulin secretion / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / peptide hormone binding / neuropeptide signaling pathway / response to immobilization stress / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / muscle contraction / protein kinase A signaling / cAMP-mediated signaling / Peptide ligand-binding receptors / secretory granule / locomotory behavior / G-protein beta/gamma-subunit complex binding / response to insulin / Olfactory Signaling Pathway / Activation of the phototransduction cascade / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / 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 / response to estrogen / 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 / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cell body / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / 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 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.3 Å | |||||||||
データ登録者 | Jiang W / Zheng S | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2022 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 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_33229.map.gz | 20.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-33229-v30.xml emd-33229.xml | 21.3 KB 21.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_33229.png | 29.3 KB | ||
その他 | emd_33229_half_map_1.map.gz emd_33229_half_map_2.map.gz | 20.6 MB 20.6 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-33229 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33229 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_33229_validation.pdf.gz | 771.5 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_33229_full_validation.pdf.gz | 771.1 KB | 表示 | |
XML形式データ | emd_33229_validation.xml.gz | 10.2 KB | 表示 | |
CIF形式データ | emd_33229_validation.cif.gz | 11.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33229 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33229 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_33229.map.gz / 形式: CCP4 / 大きさ: 22.2 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | cryoEM map of the GALR1/Go/galanin complex | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.087 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
-ハーフマップ: half map of the GALR1/Go/galanin complex
ファイル | emd_33229_half_map_1.map | ||||||||||||
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注釈 | half map of the GALR1/Go/galanin 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 the GALR1/Go/galanin complex
ファイル | emd_33229_half_map_2.map | ||||||||||||
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注釈 | half map of the GALR1/Go/galanin complex | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Galanin-bound Galanin receptor type 1 in complex with miniGalphao...
全体 | 名称: Galanin-bound Galanin receptor type 1 in complex with miniGalphao, Gbeta/gamma subunit and a single-chain variable fragment (scFv16) |
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要素 |
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-超分子 #1: Galanin-bound Galanin receptor type 1 in complex with miniGalphao...
超分子 | 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 / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: G protein subunit alpha o1,Guanine nucleotide-binding protein G(o...
分子 | 名称: G protein subunit alpha o1,Guanine nucleotide-binding protein G(o) subunit alpha タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 25.447115 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MGCTLSAEER AALERSKAIE KNLKEDGISA AKDVKLLLLG ADNSGKSTIV KQMKIIHGGS GGSGGTTGIV ETHFTFKNLH FRLFDVGGQ RSERKKWIHC FEDVTAIIFC VDLSDYNRMH ESLMLFDSIC NNKFFIDTSI ILFLNKKDLF GEKIKKSPLT I CFPEYTGP ...文字列: MGCTLSAEER AALERSKAIE KNLKEDGISA AKDVKLLLLG ADNSGKSTIV KQMKIIHGGS GGSGGTTGIV ETHFTFKNLH FRLFDVGGQ RSERKKWIHC FEDVTAIIFC VDLSDYNRMH ESLMLFDSIC NNKFFIDTSI ILFLNKKDLF GEKIKKSPLT I CFPEYTGP NTYEDAAAYI QAQFESKNRS PNKEIYCHMT CATDTNNAQV IFDAVTDIII ANNLRGCGLY UniProtKB: G protein subunit alpha o1, G protein subunit alpha o1, Guanine nucleotide-binding protein G(o) subunit alpha |
-分子 #2: 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: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 37.41693 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: Galanin
分子 | 名称: Galanin / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 3.161446 KDa |
配列 | 文字列: GWTLNSAGYL LGPHAVGNHR SFSDKNGLTS UniProtKB: Galanin peptides |
-分子 #4: Galanin receptor type 1
分子 | 名称: Galanin receptor type 1 / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 38.38293 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: DYKDDDDKGS MELAVGNLSE GNASWPEPPA PEPGPLFGIG VENFVTLVVF GLIFALGVLG NSLVITVLAR SKPGKPRSTT NLFILNLSI ADLAYLLFCI PFQATVYALP TWVLGAFICK FIHYFFTVSM LVSIFTLAAM SVDRYVAIVH SRRSSSLRVS R NALLGVGC ...文字列: DYKDDDDKGS MELAVGNLSE GNASWPEPPA PEPGPLFGIG VENFVTLVVF GLIFALGVLG NSLVITVLAR SKPGKPRSTT NLFILNLSI ADLAYLLFCI PFQATVYALP TWVLGAFICK FIHYFFTVSM LVSIFTLAAM SVDRYVAIVH SRRSSSLRVS R NALLGVGC IWALSIAMAS PVAYHQGLFH PRASNQTFCW EQWPDPRHKK AYVVCTFVFG YLLPLLLICF CYAKVLNHLH KK LKNMSKK SEASKKKTAQ TVLVVVVVFG ISWLPHHIIH LWAEFGVFPL TPASFLFRIT AHCLAYSNSS VNPIIYAFLS ENF RKAYKQ VFKCHIGGGG GGAGALEVLF Q UniProtKB: Galanin receptor type 1 |
-分子 #5: 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: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 7.845078 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFSAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #6: single Fab chain (svFv16)
分子 | 名称: single Fab chain (svFv16) / タイプ: protein_or_peptide / ID: 6 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 31.857369 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: PDVQLVESGG GLVQPGGSRK LSCSASGFAF SSFGMHWVRQ APEKGLEWVA YISSGSGTIY YADTVKGRFT ISRDDPKNTL FLQMTSLRS EDTAMYYCVR SIYYYGSSPF DFWGQGTTLT VSSGGGGSGG GGSGGGGSDI VMTQATSSVP VTPGESVSIS C RSSKSLLH ...文字列: PDVQLVESGG GLVQPGGSRK LSCSASGFAF SSFGMHWVRQ APEKGLEWVA YISSGSGTIY YADTVKGRFT ISRDDPKNTL FLQMTSLRS EDTAMYYCVR SIYYYGSSPF DFWGQGTTLT VSSGGGGSGG GGSGGGGSDI VMTQATSSVP VTPGESVSIS C RSSKSLLH SNGNTYLYWF LQRPGQSPQL LIYRMSNLAS GVPDRFSGSG SGTAFTLTIS RLEAEDVGVY YCMQHLEYPL TF GAGTKLE LKAAAGAPLE VLFQGPGAWS HPQFEKGAED QVDPRLIDGK GAAHHHHHHH H |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 5.1 mg/mL | ||||||||||
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緩衝液 | pH: 7.4 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 / 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. / 前処理 - 雰囲気: AIR / 前処理 - 気圧: 101.325 kPa | ||||||||||
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 |
-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: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
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): 2.2 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 |
-画像解析
初期モデル | モデルのタイプ: INSILICO MODEL |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 426045 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
-原子モデル構築 1
精密化 | プロトコル: RIGID BODY FIT |
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得られたモデル | PDB-7xjj: |