+
データを開く
-
基本情報
| 登録情報 | ![]() | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| タイトル | PTHrP-PTH1R-Gs complex | |||||||||
マップデータ | ||||||||||
試料 |
| |||||||||
キーワード | PTH1R / GPCR / LIPID BINDING PROTEIN-HORMONE-IMMUNE SYSTEM complex | |||||||||
| 機能・相同性 | 機能・相同性情報negative regulation of chondrocyte development / regulation of chondrocyte differentiation / adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway / parathyroid hormone receptor activity / cAMP metabolic process / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste ...negative regulation of chondrocyte development / regulation of chondrocyte differentiation / adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway / parathyroid hormone receptor activity / cAMP metabolic process / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Class B/2 (Secretin family receptors) / Vasopressin regulates renal water homeostasis via Aquaporins / G protein-coupled peptide receptor activity / negative regulation of chondrocyte differentiation / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / osteoblast development / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (12/13) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / G alpha (z) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / spectrin binding / peptide hormone receptor binding / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / bone mineralization / alkylglycerophosphoethanolamine phosphodiesterase activity / positive regulation of inositol phosphate biosynthetic process / peptide hormone binding / epidermis development / chondrocyte differentiation / photoreceptor outer segment / bone resorption / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / cardiac muscle cell apoptotic process / cell maturation / photoreceptor inner segment / skeletal system development / female pregnancy / hormone activity / G protein-coupled receptor activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / intracellular calcium ion homeostasis / cellular response to catecholamine stimulus / cell-cell signaling / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G-protein beta-subunit binding / sensory perception of taste / adenylate cyclase-activating G protein-coupled receptor signaling pathway / signaling receptor complex adaptor activity / positive regulation of cytosolic calcium ion concentration / retina development in camera-type eye / regulation of gene expression / cell body / GTPase binding / cellular response to hypoxia / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / in utero embryonic development / basolateral plasma membrane / cell surface receptor signaling pathway / cell population proliferation / signaling receptor complex / apical plasma membrane / G protein-coupled receptor signaling pathway 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: 3.25 Å | |||||||||
データ登録者 | Zhao L / Xu HE / Yuan Q | |||||||||
| 資金援助 | 中国, 1件
| |||||||||
引用 | ジャーナル: Acta Pharmacol Sin / 年: 2023タイトル: Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1. 著者: Li-Hua Zhao / Qing-Ning Yuan / An-Tao Dai / Xin-Heng He / Chuan-Wei Chen / Chao Zhang / You-Wei Xu / Yan Zhou / Ming-Wei Wang / De-Hua Yang / H Eric Xu / ![]() 要旨: Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor-1 (PTH1R), a member of class B G protein- coupled receptors (GPCRs). Both PTH and ...Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor-1 (PTH1R), a member of class B G protein- coupled receptors (GPCRs). Both PTH and PTHrP analogs including teriparatide and abaloparatide are approved drugs for osteoporosis, but they exhibit distinct pharmacology. Here we report two cryo-EM structures of human PTH1R bound to PTH and PTHrP in the G protein-bound state at resolutions of 2.62 Å and 3.25 Å, respectively. Detailed analysis of these structures uncovers both common and unique features for the agonism of PTH and PTHrP. Molecular dynamics (MD) simulation together with site-directed mutagenesis studies reveal the molecular basis of endogenous hormones recognition specificity and selectivity to PTH1R. These results provide a rational template for the clinical use of PTH and PTHrP analogs as an anabolic therapy for osteoporosis and other disorders. | |||||||||
| 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_34587.map.gz | 91.4 MB | EMDBマップデータ形式 | |
|---|---|---|---|---|
| ヘッダ (付随情報) | emd-34587-v30.xml emd-34587.xml | 24.7 KB 24.7 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_34587.png | 30.2 KB | ||
| Filedesc metadata | emd-34587.cif.gz | 7.4 KB | ||
| その他 | emd_34587_half_map_1.map.gz emd_34587_half_map_2.map.gz | 81 MB 81 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-34587 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34587 | 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_34587.map.gz / 形式: CCP4 / 大きさ: 103 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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: 0.824 Å | ||||||||||||||||||||||||||||||||||||
| 密度 |
| ||||||||||||||||||||||||||||||||||||
| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
|
-添付データ
-ハーフマップ: #2
| ファイル | emd_34587_half_map_1.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 投影像・断面図 |
| ||||||||||||
| 密度ヒストグラム |
-ハーフマップ: #1
| ファイル | emd_34587_half_map_2.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 投影像・断面図 |
| ||||||||||||
| 密度ヒストグラム |
-
試料の構成要素
-全体 : PTH-PTHR G protein complex
| 全体 | 名称: PTH-PTHR G protein complex |
|---|---|
| 要素 |
|
-超分子 #1: PTH-PTHR G protein complex
| 超分子 | 名称: PTH-PTHR G protein complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6 |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha-1
| 分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha-1 タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 41.879465 KDa |
| 組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
| 配列 | 文字列: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RATHRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RATHRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTSGIFETK FQVDKVNFHM FDVGAQRDER RKWIQCFNDV TAIIFVVDSS DYNRLQEALN DF KSIWNNR WLRTISVILF LNKQDLLAEK VLAGKSKIED YFPEFARYTT PEDATPEPGE DPRVTRAKYF IRDEFLRIST ASG DGRHYC YPHFTCSVDT ENARRIFNDC RDIIQRMHLR QYELL |
-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 |
|---|---|
| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 43.70675 KDa |
| 組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
| 配列 | 文字列: MHHHHHHSSG LVPRGSHMAS HHHHHHHHHH GSLLQSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN L KTREGNVR ...文字列: MHHHHHHSSG LVPRGSHMAS HHHHHHHHHH GSLLQSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN L KTREGNVR VSRELAGHTG YLSCCRFLDD NQIVTSSGDT TCALWDIETG QQTTTFTGHT GDVMSLSLAP DTRLFVSGAC DA SAKLWDV REGMCRQTFT GHESDINAIC FFPNGNAFAT GSDDATCRLF DLRADQELMT YSHDNIICGI TSVSFSKSGR LLL AGYDDF NCNVWDALKA DRAGVLAGHD NRVSCLGVTD DGMAVATGSW DSFLKIWNGS SGGGGSGGGG SSGVSGWRLF KKIS UniProtKB: 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 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 7.861143 KDa |
| 組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
| 配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: Nanobody 35
| 分子 | 名称: Nanobody 35 / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: synthetic construct (人工物) |
| 分子量 | 理論値: 15.343019 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MAQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGRF TISRDNAKNT LYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SHHHHHHEPE A |
-分子 #5: PTHrP[1-36]
| 分子 | 名称: PTHrP[1-36] / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 4.267916 KDa |
| 組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
| 配列 | 文字列: AVSEHQLLHD KGKSIQDLRR RFFLHHLIAE IHTAEI(NH2) UniProtKB: Parathyroid hormone-related protein |
-分子 #6: Parathyroid hormone/parathyroid hormone-related peptide receptor
| 分子 | 名称: Parathyroid hormone/parathyroid hormone-related peptide receptor タイプ: protein_or_peptide / ID: 6 / コピー数: 1 / 光学異性体: LEVO |
|---|---|
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 54.506734 KDa |
| 組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
| 配列 | 文字列: DADDVMTKEE QIFLLHRAQA QCEKRLKEVL QRPASIMESD KGWTSASTSG KPRKDKASGK LYPESEEDKE APTGSRYRGR PCLPEWDHI LCWPLGAPGE VVAVPCPDYI YDFNHKGHAY RRCDRNGSWE LVPGHNRTWA NYSECVKFLT NETREREVFD R LAMIYTVG ...文字列: DADDVMTKEE QIFLLHRAQA QCEKRLKEVL QRPASIMESD KGWTSASTSG KPRKDKASGK LYPESEEDKE APTGSRYRGR PCLPEWDHI LCWPLGAPGE VVAVPCPDYI YDFNHKGHAY RRCDRNGSWE LVPGHNRTWA NYSECVKFLT NETREREVFD R LAMIYTVG YSVSLASLTV AVLILAYFRR LHCTRNYIHM HLFLSFMLRA VSIFVKDAVL YSGATLDEAE RLTEEELRAI AQ APPPPAT AAAGYAGCRV AVTFFLYFLA TNYYWILVEG LYLHSLIFMA FFSEKKYLWG FTVFGWGLPA VFVAVWVSVR ATL ANTGCW DLSSGNKKWI IQVPILASIV LNFILFINIV RVLATKLRET NAGRCDTRQQ YRKLLKSTLV LMPLFGVHYI VFMA TPYTE VSGTLWQVQM HYEMLFNSFQ GFFVAIIYCF CNGEVQAEIK KSWSRWTLAL DFRRKARSGS SSYSYGPMVS H UniProtKB: Parathyroid hormone/parathyroid hormone-related peptide receptor |
-分子 #7: PALMITIC ACID
| 分子 | 名称: PALMITIC ACID / タイプ: ligand / ID: 7 / コピー数: 11 / 式: PLM |
|---|---|
| 分子量 | 理論値: 256.424 Da |
| Chemical component information | ![]() ChemComp-PLM: |
-分子 #8: CHOLESTEROL
| 分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 8 / コピー数: 6 / 式: CLR |
|---|---|
| 分子量 | 理論値: 386.654 Da |
| Chemical component information | ![]() ChemComp-CLR: |
-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
| 緩衝液 | pH: 7.4 |
|---|---|
| 凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % |
-
電子顕微鏡法
| 顕微鏡 | FEI TITAN KRIOS |
|---|---|
| 温度 | 最低: 89.0 K / 最高: 100.0 K |
| 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 | C2レンズ絞り径: 50.0 µm / 最大 デフォーカス(補正後): 2.2 µm / 最小 デフォーカス(補正後): 0.6 µm / 倍率(補正後): 105000 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 1.8 µm / 最小 デフォーカス(公称値): 0.8 µm / 倍率(公称値): 105000 |
| 試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
ムービー
コントローラー
万見について




キーワード
Homo sapiens (ヒト)
データ登録者
中国, 1件
引用

















Z (Sec.)
Y (Row.)
X (Col.)




































Trichoplusia ni (イラクサキンウワバ)


解析
FIELD EMISSION GUN
