+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-27872 | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of the PAC1R-PACAP27-Gs complex | ||||||||||||||||||
マップデータ | Consensus map of PAC1R-PACAP27-Gs complex, postprocessed, -25 B factor sharpened | ||||||||||||||||||
試料 |
| ||||||||||||||||||
キーワード | membrane protein / drug discovery / G protein coupled receptor / signalling | ||||||||||||||||||
機能・相同性 | 機能・相同性情報 negative regulation of response to reactive oxygen species / development of primary female sexual characteristics / pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of growth hormone secretion / positive regulation of cAMP-mediated signaling / NGF-independant TRKA activation / regulation of G protein-coupled receptor signaling pathway / neuropeptide hormone activity ...negative regulation of response to reactive oxygen species / development of primary female sexual characteristics / pituitary adenylate cyclase activating polypeptide activity / vasoactive intestinal polypeptide receptor activity / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of growth hormone secretion / positive regulation of cAMP-mediated signaling / NGF-independant TRKA activation / regulation of G protein-coupled receptor signaling pathway / neuropeptide hormone activity / G protein-coupled peptide receptor activity / positive regulation of small GTPase mediated signal transduction / neuropeptide binding / insulin secretion / positive regulation of inositol phosphate biosynthetic process / positive regulation of calcium ion transport into cytosol / peptide hormone receptor binding / PKA activation in glucagon signalling / peptide hormone binding / adenylate cyclase binding / hair follicle placode formation / negative regulation of cell cycle / developmental growth / neuropeptide signaling pathway / D1 dopamine receptor binding / bicellular tight junction / multicellular organismal response to stress / positive regulation of protein kinase activity / intracellular transport / renal water homeostasis / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / cellular response to glucagon stimulus / cAMP-mediated signaling / adenylate cyclase activator activity / regulation of insulin secretion / positive regulation of GTPase activity / trans-Golgi network membrane / female pregnancy / negative regulation of inflammatory response to antigenic stimulus / bone development / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / caveola / Activation of the phototransduction cascade / adenylate cyclase-activating 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-coupled acetylcholine receptor signaling pathway / G protein activity / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / platelet aggregation / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / small GTPase binding / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / cellular response to prostaglandin E stimulus / neuron projection development / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / sensory perception of smell / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / cell-cell signaling / GTPase binding / response to estradiol / positive regulation of cold-induced thermogenesis / regulation of protein localization / retina development in camera-type eye / signaling receptor activity / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration 類似検索 - 分子機能 | ||||||||||||||||||
生物種 | Homo sapiens (ヒト) / Lama glama (ラマ) | ||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.3 Å | ||||||||||||||||||
データ登録者 | Piper SJ / Danev R / Sexton P / Wootten D | ||||||||||||||||||
資金援助 | オーストラリア, 英国, 日本, 5件
| ||||||||||||||||||
引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Understanding VPAC receptor family peptide binding and selectivity. 著者: Sarah J Piper / Giuseppe Deganutti / Jessica Lu / Peishen Zhao / Yi-Lynn Liang / Yao Lu / Madeleine M Fletcher / Mohammed Akhter Hossain / Arthur Christopoulos / Christopher A Reynolds / ...著者: Sarah J Piper / Giuseppe Deganutti / Jessica Lu / Peishen Zhao / Yi-Lynn Liang / Yao Lu / Madeleine M Fletcher / Mohammed Akhter Hossain / Arthur Christopoulos / Christopher A Reynolds / Radostin Danev / Patrick M Sexton / Denise Wootten / 要旨: The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are key regulators of neurological processes. Despite recent structural data, a ...The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are key regulators of neurological processes. Despite recent structural data, a comprehensive understanding of peptide binding and selectivity among different subfamily receptors is lacking. Here, we determine structures of active, Gs-coupled, VIP-VPAC1R, PACAP27-VPAC1R, and PACAP27-PAC1R complexes. Cryo-EM structural analyses and molecular dynamics simulations (MDSs) reveal fewer stable interactions between VPAC1R and VIP than for PACAP27, more extensive dynamics of VIP interaction with extracellular loop 3, and receptor-dependent differences in interactions of conserved N-terminal peptide residues with the receptor core. MD of VIP modelled into PAC1R predicts more transient VIP-PAC1R interactions in the receptor core, compared to VIP-VPAC1R, which may underlie the selectivity of VIP for VPAC1R over PAC1R. Collectively, our work improves molecular understanding of peptide engagement with the PAC1R and VPAC1R that may benefit the development of novel selective agonists. | ||||||||||||||||||
履歴 |
|
-構造の表示
添付画像 |
---|
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_27872.map.gz | 84 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-27872-v30.xml emd-27872.xml | 32 KB 32 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_27872_fsc.xml | 10.2 KB | 表示 | FSCデータファイル |
画像 | emd_27872.png | 65.1 KB | ||
マスクデータ | emd_27872_msk_1.map | 91.1 MB | マスクマップ | |
Filedesc metadata | emd-27872.cif.gz | 7.1 KB | ||
その他 | emd_27872_additional_1.map.gz emd_27872_additional_2.map.gz emd_27872_additional_3.map.gz emd_27872_additional_4.map.gz emd_27872_half_map_1.map.gz emd_27872_half_map_2.map.gz | 71 MB 8.2 MB 3.1 MB 44.1 MB 71.2 MB 71.2 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-27872 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27872 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_27872_validation.pdf.gz | 770.2 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_27872_full_validation.pdf.gz | 769.7 KB | 表示 | |
XML形式データ | emd_27872_validation.xml.gz | 17.6 KB | 表示 | |
CIF形式データ | emd_27872_validation.cif.gz | 23.1 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27872 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27872 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「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_27872.map.gz / 形式: CCP4 / 大きさ: 91.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Consensus map of PAC1R-PACAP27-Gs complex, postprocessed, -25 B factor sharpened | ||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-マスク #1
ファイル | emd_27872_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-追加マップ: Consensus map of PAC1R-PACAP27-Gs complex, refinement map
ファイル | emd_27872_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Consensus map of PAC1R-PACAP27-Gs complex, refinement map | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-追加マップ: Consensus map of PAC1R-PACAP27-Gs complex, postprocessed, -25 B...
ファイル | emd_27872_additional_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Consensus map of PAC1R-PACAP27-Gs complex, postprocessed, -25 B factor sharpened | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-追加マップ: Receptor focused map of PAC1R-PACAP27-Gs complex
ファイル | emd_27872_additional_3.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Receptor focused map of PAC1R-PACAP27-Gs complex | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-追加マップ: CryoSPARC non-uniform refinement map of PAC1R-PACAP27-Gs complex
ファイル | emd_27872_additional_4.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | CryoSPARC non-uniform refinement map of PAC1R-PACAP27-Gs complex | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: Half map 1 of Consensus refinement of PAC1R-PACAP27-Gs complex
ファイル | emd_27872_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Half map 1 of Consensus refinement of PAC1R-PACAP27-Gs complex | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: Half map 2 of Consensus refinement of PAC1R-PACAP27-Gs complex
ファイル | emd_27872_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Half map 2 of Consensus refinement of PAC1R-PACAP27-Gs complex | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-試料の構成要素
+全体 : Gs coupled Pituitary adenylate cyclase-activating polypeptide typ...
+超分子 #1: Gs coupled Pituitary adenylate cyclase-activating polypeptide typ...
+超分子 #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
+超分子 #3: Nanobody35
+超分子 #4: Pituitary adenylate cyclase activating polypeptide-27
+分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #4: Nanobody35
+分子 #5: Pituitary adenylate cyclase-activating polypeptide
+分子 #6: Pituitary adenylate cyclase-activating polypeptide type I receptor
+分子 #7: water
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 5.15 mg/mL |
---|---|
緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 検出モード: COUNTING / 平均電子線量: 52.4 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): 1.4000000000000001 µm 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |