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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 7vvm | ||||||
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タイトル | PTH-bound human PTH1R in complex with Gs (class3) | ||||||
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![]() | SIGNALING PROTEIN / G protein-coupled receptor / membrane protein | ||||||
機能・相同性 | ![]() type 1 parathyroid hormone receptor binding / parathyroid hormone receptor binding / negative regulation of bone mineralization involved in bone maturation / positive regulation of osteoclast proliferation / negative regulation of apoptotic process in bone marrow cell / hormone-mediated apoptotic signaling pathway / response to parathyroid hormone / parathyroid hormone receptor activity / positive regulation of cell proliferation in bone marrow / magnesium ion homeostasis ...type 1 parathyroid hormone receptor binding / parathyroid hormone receptor binding / negative regulation of bone mineralization involved in bone maturation / positive regulation of osteoclast proliferation / negative regulation of apoptotic process in bone marrow cell / hormone-mediated apoptotic signaling pathway / response to parathyroid hormone / parathyroid hormone receptor activity / positive regulation of cell proliferation in bone marrow / magnesium ion homeostasis / positive regulation of signal transduction / macromolecule biosynthetic process / response to fibroblast growth factor / phosphate ion homeostasis / 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 / response to vitamin D / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G protein-coupled peptide receptor activity / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / negative regulation of chondrocyte differentiation / G alpha (i) signalling events / Class B/2 (Secretin family receptors) / 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 / Glucagon-type ligand receptors / alkylglycerophosphoethanolamine phosphodiesterase activity / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / osteoblast development / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / positive regulation of inositol phosphate biosynthetic process / peptide hormone receptor binding / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / bone mineralization / peptide hormone binding / PKA activation in glucagon signalling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / Rho protein signal transduction / : / hair follicle placode formation / photoreceptor outer segment / mu-type opioid receptor binding / developmental growth / positive regulation of glycogen biosynthetic process / corticotropin-releasing hormone receptor 1 binding / intracellular transport / D1 dopamine receptor binding / Hedgehog 'off' state / chondrocyte differentiation / positive regulation of bone mineralization / response to cadmium ion / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / cell maturation / homeostasis of number of cells within a tissue / bone resorption / cardiac muscle cell apoptotic process / activation of adenylate cyclase activity / adenylate cyclase activator activity / photoreceptor inner segment / trans-Golgi network membrane / skeletal system development / positive regulation of glucose import / response to lead ion 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() ![]() ![]() ![]() unidentified (未定義) | ||||||
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: 3.2 Å | ||||||
![]() | Kobayashi, K. / Kusakizako, T. / Miyauchi, H. / Tomita, A. / Kobayashi, K. / Shihoya, W. / Yamashita, K. / Nishizawa, T. / Kato, H.E. / Nureki, O. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Endogenous ligand recognition and structural transition of a human PTH receptor. 著者: Kazuhiro Kobayashi / Kouki Kawakami / Tsukasa Kusakizako / Hirotake Miyauchi / Atsuhiro Tomita / Kan Kobayashi / Wataru Shihoya / Keitaro Yamashita / Tomohiro Nishizawa / Hideaki E Kato / ...著者: Kazuhiro Kobayashi / Kouki Kawakami / Tsukasa Kusakizako / Hirotake Miyauchi / Atsuhiro Tomita / Kan Kobayashi / Wataru Shihoya / Keitaro Yamashita / Tomohiro Nishizawa / Hideaki E Kato / Asuka Inoue / Osamu Nureki / ![]() 要旨: Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. Intriguingly, ...Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas PTHrP evokes transient Gs activation with reduced bone-resorption effects. The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation kinetics. Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the presence of PTH or PTHrP at resolutions of 2.8 -4.1 Å. A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. Furthermore, five distinct PTH-bound structures, combined with computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH and PTHrP. | ||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 233.3 KB | 表示 | ![]() |
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PDB形式 | ![]() | 178 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 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.1 MB | 表示 | |
XML形式データ | ![]() | 41.1 KB | 表示 | |
CIF形式データ | ![]() | 62.8 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 | ![]() 32144MC ![]() 7vvjC ![]() 7vvkC ![]() 7vvlC ![]() 7vvnC ![]() 7vvoC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABG
#1: タンパク質 | 分子量: 44255.664 Da / 分子数: 1 / 変異: G45E, E46N, L59Y, A245D, S248D, H358A, C361I / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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#2: タンパク質 | 分子量: 38744.371 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: P54311 |
#3: タンパク質 | 分子量: 7547.685 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: P63212 |
-抗体 / タンパク質・ペプチド / タンパク質 , 3種, 3分子 NPR
#4: 抗体 | 分子量: 15015.728 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) unidentified (未定義) / 発現宿主: ![]() ![]() |
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#5: タンパク質・ペプチド | 分子量: 4125.778 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) ![]() |
#6: タンパク質 | 分子量: 54264.359 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
-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 |
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試料調製
構成要素 |
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分子量 | 実験値: NO | ||||||||||||||||||||||||||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.4 | ||||||||||||||||||||||||||||||||||||||||||||||||
試料 | 濃度: 10 mg/ml / 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 |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1500 nm / 最小 デフォーカス(公称値): 600 nm |
撮影 | 電子線照射量: 64.319 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
ソフトウェア | 名称: REFMAC / バージョン: 5.8.0298 / 分類: 精密化 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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CTF補正 | タイプ: NONE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 73994 / 対称性のタイプ: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化 | 解像度: 3.2→135.01 Å / Cor.coef. Fo:Fc: 0.882 / SU B: 18.279 / SU ML: 0.295 / ESU R: 0.345 立体化学のターゲット値: MAXIMUM LIKELIHOOD WITH PHASES 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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溶媒の処理 | 溶媒モデル: PARAMETERS FOR MASK CACLULATION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 99.266 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: 1 / 合計: 8509 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
拘束条件 |
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