+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8hao | ||||||
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タイトル | Human parathyroid hormone receptor-1 dimer | ||||||
要素 |
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キーワード | LIPID BINDING PROTEIN/HORMONE/IMMUNE SYSTEM / PTH1R / GPCR / LIPID BINDING PROTEIN-HORMONE-IMMUNE SYSTEM complex | ||||||
機能・相同性 | 機能・相同性情報 parathyroid hormone receptor binding / type 1 parathyroid hormone receptor binding / negative regulation of bone mineralization involved in bone maturation / negative regulation of apoptotic process in bone marrow cell / positive regulation of osteoclast proliferation / response to parathyroid hormone / macromolecule biosynthetic process / parathyroid hormone receptor activity / hormone-mediated apoptotic signaling pathway / positive regulation of cell proliferation in bone marrow ...parathyroid hormone receptor binding / type 1 parathyroid hormone receptor binding / negative regulation of bone mineralization involved in bone maturation / negative regulation of apoptotic process in bone marrow cell / positive regulation of osteoclast proliferation / response to parathyroid hormone / macromolecule biosynthetic process / parathyroid hormone receptor activity / hormone-mediated apoptotic signaling pathway / positive regulation of cell proliferation in bone marrow / positive regulation of signal transduction / magnesium ion homeostasis / response to fibroblast growth factor / phosphate ion homeostasis / cAMP metabolic process / response to vitamin D / G protein-coupled peptide receptor activity / negative regulation of chondrocyte differentiation / Class B/2 (Secretin family receptors) / 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 / Glucagon-type ligand receptors / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / osteoblast development / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / positive regulation of inositol phosphate biosynthetic process / peptide hormone receptor binding / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / bone mineralization / peptide hormone binding / Rho protein signal transduction / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of glycogen biosynthetic process / chondrocyte differentiation / bone resorption / response to cadmium ion / positive regulation of bone mineralization / cell maturation / homeostasis of number of cells within a tissue / skeletal system development / positive regulation of D-glucose import / adenylate cyclase-activating G protein-coupled receptor signaling pathway / response to lead ion / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / hormone activity / intracellular calcium ion homeostasis / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / cell-cell signaling / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (s) signalling events / regulation of gene expression / basolateral plasma membrane / in utero embryonic development / response to ethanol / transcription by RNA polymerase II / cell population proliferation / receptor complex / cell surface receptor signaling pathway / receptor ligand activity / response to xenobiotic stimulus / G protein-coupled receptor signaling pathway / apical plasma membrane / negative regulation of cell population proliferation / negative regulation of gene expression / GTPase activity / positive regulation of cell population proliferation / positive regulation of gene expression / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / membrane / nucleus / plasma membrane / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | Bos taurus (ウシ) Rattus norvegicus (ドブネズミ) synthetic construct (人工物) Homo sapiens (ヒト) | ||||||
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: 3.76 Å | ||||||
データ登録者 | Zhao, L. / Xu, H.E. / Yuan, Q. | ||||||
資金援助 | 中国, 1件
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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 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8hao.cif.gz | 418.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8hao.ent.gz | 339 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8hao.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 8hao_validation.pdf.gz | 1.3 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8hao_full_validation.pdf.gz | 1.3 MB | 表示 | |
XML形式データ | 8hao_validation.xml.gz | 74.1 KB | 表示 | |
CIF形式データ | 8hao_validation.cif.gz | 108.3 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ha/8hao ftp://data.pdbj.org/pub/pdb/validation_reports/ha/8hao | HTTPS FTP |
-関連構造データ
関連構造データ | 34598MC 8ha0C 8hafC 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 6分子 ACBDEG
#1: タンパク質 | 分子量: 41879.465 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Bos taurus (ウシ) / 発現宿主: Trichoplusia ni (イラクサキンウワバ) #2: タンパク質 | 分子量: 43706.750 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) / 発現宿主: Trichoplusia ni (イラクサキンウワバ) #3: タンパク質 | 分子量: 7861.143 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Bos taurus (ウシ) / 遺伝子: GNG2 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P63212 |
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-抗体 / タンパク質・ペプチド / タンパク質 , 3種, 6分子 FNHPIR
#4: 抗体 | 分子量: 15343.019 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) synthetic construct (人工物) / 発現宿主: Escherichia coli (大腸菌) #5: タンパク質・ペプチド | 分子量: 4123.786 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PTH / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P01270 #6: タンパク質 | 分子量: 54506.734 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PTH1R, PTHR, PTHR1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: Q03431 |
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-詳細
Has protein modification | 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 |
-試料調製
構成要素 | 名称: PTH-PTHR G protein complex / タイプ: COMPLEX / Entity ID: all / 由来: MULTIPLE SOURCES |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Trichoplusia ni (イラクサキンウワバ) |
緩衝液 | pH: 7.4 |
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 / 湿度: 100 % |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 105000 X / 倍率(補正後): 105000 X / 最大 デフォーカス(公称値): 1800 nm / 最小 デフォーカス(公称値): 800 nm / Calibrated defocus min: 600 nm / 最大 デフォーカス(補正後): 2200 nm / Cs: 2.7 mm / C2レンズ絞り径: 50 µm |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER 最高温度: 100 K / 最低温度: 89 K |
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
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 3.76 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 55858 / 対称性のタイプ: POINT |