登録情報 データベース : PDB / ID : 6nbi 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein 要素(Guanine nucleotide-binding protein ...) x 2 Gs protein alpha subunit Long-acting parathyroid hormone analog Nanobody-35 ナノボディ Parathyroid hormone/parathyroid hormone-related peptide receptor 詳細キーワード SIGNALING PROTEIN / Parathyroid hormone receptor / GPCR (Gタンパク質共役受容体) / Class B GPCR / GPCR-G protein complex機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
parathyroid hormone receptor activity / sensory perception of chemical stimulus / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / 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 ... parathyroid hormone receptor activity / sensory perception of chemical stimulus / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / 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 / Ca2+ pathway / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / 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 / 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 / beta-2 adrenergic receptor binding / G alpha (q) signalling events / positive regulation of inositol phosphate biosynthetic process / 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 / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / photoreceptor outer segment / D1 dopamine receptor binding / positive regulation of cAMP-mediated signaling / chondrocyte differentiation / adenylate cyclase-activating adrenergic receptor signaling pathway / cell maturation / bone resorption / cardiac muscle cell apoptotic process / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / adenylate cyclase activator activity / photoreceptor inner segment / skeletal system development / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of GTPase activity / cellular response to catecholamine stimulus / intracellular calcium ion homeostasis / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / : / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / phospholipase C-activating G protein-coupled receptor signaling pathway / cell body / positive regulation of cytosolic calcium ion concentration / cellular response to hypoxia / G alpha (s) signalling events / basolateral plasma membrane / in utero embryonic development / cell population proliferation / cell surface receptor signaling pathway / receptor complex / apical plasma membrane / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation 類似検索 - 分子機能 GPCR, family 2, parathyroid hormone receptor / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / G-protein coupled receptors family 2 signature 1. / Hormone receptor domain / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. / Domain present in hormone receptors / GPCR family 2, extracellular hormone receptor domain superfamily / G-protein coupled receptors family 2 signature 2. ... GPCR, family 2, parathyroid hormone receptor / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / G-protein coupled receptors family 2 signature 1. / Hormone receptor domain / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. / Domain present in hormone receptors / GPCR family 2, extracellular hormone receptor domain superfamily / G-protein coupled receptors family 2 signature 2. / GPCR, family 2, secretin-like, conserved site / GPCR, family 2, secretin-like / 7 transmembrane receptor (Secretin family) / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. / G-protein alpha subunit, group S / YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / Few Secondary Structures / イレギュラー / G-protein beta WD-40 repeat / P-loop containing nucleotide triphosphate hydrolases / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40リピート / WD40リピート / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase / ロスマンフォールド / 3-Layer(aba) Sandwich / Mainly Beta / Alpha Beta 類似検索 - ドメイン・相同性 コレステロール / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Parathyroid hormone/parathyroid hormone-related peptide receptor 類似検索 - 構成要素生物種 Homo sapiens (ヒト)Bos taurus (ウシ)Rattus norvegicus (ドブネズミ)synthetic construct (人工物) 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 : 4 Å 詳細データ登録者 Zhao, L.-H. / Ma, S. / Sutkeviciute, I. / Shen, D.-D. / Zhou, X.E. / de Waal, P.P. / Li, C.-Y. / Kang, Y. / Clark, L.J. / Jean-Alphonse, F.G. ...Zhao, L.-H. / Ma, S. / Sutkeviciute, I. / Shen, D.-D. / Zhou, X.E. / de Waal, P.P. / Li, C.-Y. / Kang, Y. / Clark, L.J. / Jean-Alphonse, F.G. / White, A.D. / Xiao, K. / Yang, D. / Jiang, Y. / Watanabe, T. / Gardella, T.J. / Melcher, K. / Wang, M.-W. / Vilardaga, J.-P. / Xu, H.E. / Zhang, Y. 資金援助 中国, 米国, 5件 詳細 詳細を隠す組織 認可番号 国 National Science Foundation (NSF, China) Shanghai 18ZR1447800 中国 National Natural Science Foundation of China (NSFC) 31300245 中国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) GM127710 米国 National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK) DK102495, DK111427, DK116780 米国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) 008424 米国
引用ジャーナル : Science / 年 : 2019タイトル : Structure and dynamics of the active human parathyroid hormone receptor-1.著者: Li-Hua Zhao / Shanshan Ma / Ieva Sutkeviciute / Dan-Dan Shen / X Edward Zhou / Parker W de Waal / Chen-Yao Li / Yanyong Kang / Lisa J Clark / Frederic G Jean-Alphonse / Alex D White / Dehua ... 著者 : Li-Hua Zhao / Shanshan Ma / Ieva Sutkeviciute / Dan-Dan Shen / X Edward Zhou / Parker W de Waal / Chen-Yao Li / Yanyong Kang / Lisa J Clark / Frederic G Jean-Alphonse / Alex D White / Dehua Yang / Antao Dai / Xiaoqing Cai / Jian Chen / Cong Li / Yi Jiang / Tomoyuki Watanabe / Thomas J Gardella / Karsten Melcher / Ming-Wei Wang / Jean-Pierre Vilardaga / H Eric Xu / Yan Zhang / 要旨 : The parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to calcium homeostasis and a therapeutic target for osteoporosis and hypoparathyroidism. Here we report the ... The parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to calcium homeostasis and a therapeutic target for osteoporosis and hypoparathyroidism. Here we report the cryo-electron microscopy structure of human PTH1R bound to a long-acting PTH analog and the stimulatory G protein. The bound peptide adopts an extended helix with its amino terminus inserted deeply into the receptor transmembrane domain (TMD), which leads to partial unwinding of the carboxyl terminus of transmembrane helix 6 and induces a sharp kink at the middle of this helix to allow the receptor to couple with G protein. In contrast to a single TMD structure state, the extracellular domain adopts multiple conformations. These results provide insights into the structural basis and dynamics of PTH binding and receptor activation. 履歴 登録 2018年12月7日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2019年4月17日 Provider : repository / タイプ : Initial release改定 1.1 2019年4月24日 Group : Data collection / Database references / カテゴリ : citation / citation_authorItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title 改定 1.2 2019年12月18日 Group : Author supporting evidence / Other / カテゴリ : atom_sites / pdbx_audit_supportItem : _atom_sites.fract_transf_matrix[1][1] / _atom_sites.fract_transf_matrix[2][2] ... _atom_sites.fract_transf_matrix[1][1] / _atom_sites.fract_transf_matrix[2][2] / _atom_sites.fract_transf_matrix[3][3] / _pdbx_audit_support.funding_organization
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