登録情報 データベース : EMDB / ID : EMD-13141 構造の表示 ダウンロードとリンクタイトル Human Neurokinin 1 receptor (NK1R) substance P Gs complex マップデータprocessed map 詳細 試料複合体 : NK1R in complex with Substance P, heterotrimeric mini-Gs chimera (Gsi) and scFv16タンパク質・ペプチド : Antibody fragment scFv16タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2タンパク質・ペプチド : Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s) subunit alpha isoforms shortタンパク質・ペプチド : Substance-P receptorタンパク質・ペプチド : Protachykinin-1 残り2件を表示 表示を減らすリガンド : CHOLESTEROL 詳細機能・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
substance P receptor binding / substance P receptor activity / insemination / tachykinin receptor activity / aggressive behavior / Tachykinin receptors bind tachykinins / positive regulation of flagellated sperm motility / positive regulation of uterine smooth muscle contraction / detection of abiotic stimulus / positive regulation of synaptic transmission, cholinergic ... substance P receptor binding / substance P receptor activity / insemination / tachykinin receptor activity / aggressive behavior / Tachykinin receptors bind tachykinins / positive regulation of flagellated sperm motility / positive regulation of uterine smooth muscle contraction / detection of abiotic stimulus / positive regulation of synaptic transmission, cholinergic / tachykinin receptor signaling pathway / operant conditioning / positive regulation of lymphocyte proliferation / sperm head / response to ozone / sperm ejaculation / positive regulation of action potential / response to auditory stimulus / smooth muscle contraction involved in micturition / regulation of smooth muscle cell proliferation / positive regulation of hormone secretion / positive regulation of blood pressure / positive regulation of vascular permeability / positive regulation of ossification / regulation of smooth muscle cell migration / positive regulation of leukocyte migration / eating behavior / response to pain / positive regulation of epithelial cell migration / behavioral response to pain / associative learning / PKA activation in glucagon signalling / angiotensin-mediated drinking behavior / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / intracellular transport / D1 dopamine receptor binding / sperm flagellum / Adenylate cyclase inhibitory pathway / neuropeptide signaling pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / Hedgehog 'off' state / D2 dopamine receptor binding / long-term memory / G protein-coupled serotonin receptor binding / response to electrical stimulus / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of mitotic spindle organization / cellular response to forskolin / positive regulation of vasoconstriction / sensory perception of pain / sperm midpiece / positive regulation of stress fiber assembly / activation of adenylate cyclase activity / adenylate cyclase activator activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cellular response to nerve growth factor stimulus / trans-Golgi network membrane / positive regulation of epithelial cell proliferation / Regulation of insulin secretion / response to progesterone / G protein-coupled receptor binding / positive regulation of synaptic transmission, GABAergic / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / response to nicotine / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / response to peptide hormone / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion 類似検索 - 分子機能 Tachykinin family / Tachykinin family / Tachykinin domain / Tachykinin family / Neurokinin NK1 receptor / Neurokinin receptor / Tachykinin/Neurokinin-like, conserved site / Tachykinin family signature. / G-protein alpha subunit, group S / G-protein alpha subunit, group I ... Tachykinin family / Tachykinin family / Tachykinin domain / Tachykinin family / Neurokinin NK1 receptor / Neurokinin receptor / Tachykinin/Neurokinin-like, conserved site / Tachykinin family signature. / G-protein alpha subunit, group S / G-protein alpha subunit, group I / 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 / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / G-protein beta WD-40 repeat / 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 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Protachykinin-1 / Substance-P receptor / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / Guanine nucleotide-binding protein G(i) subunit alpha-1 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Mus musculus (ハツカネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.87 Å 詳細 データ登録者Thom C / Ehrenmann J / Vacca S / Waltenspuhl Y / Schoppe J / Medalia O / Pluckthun A 資金援助 スイス, 2件 詳細 詳細を隠すOrganization Grant number 国 Swiss National Science Foundation 31003A_182334 スイス European Research Council (ERC) 810057-HighResCells スイス
引用ジャーナル : Sci Adv / 年 : 2021タイトル : Structures of neurokinin 1 receptor in complex with G and G proteins reveal substance P binding mode and unique activation features.著者 : Cristian Thom / Janosch Ehrenmann / Santiago Vacca / Yann Waltenspühl / Jendrik Schöppe / Ohad Medalia / Andreas Plückthun / 要旨 : The neurokinin 1 receptor (NKR) is involved in inflammation and pain transmission. This pathophysiologically important G protein–coupled receptor is predominantly activated by its cognate agonist ... The neurokinin 1 receptor (NKR) is involved in inflammation and pain transmission. This pathophysiologically important G protein–coupled receptor is predominantly activated by its cognate agonist substance P (SP) but also by the closely related neurokinins A and B. Here, we report cryo–electron microscopy structures of SP-bound NKR in complex with its primary downstream signal mediators, G and G. Our structures reveal how a polar network at the extracellular, solvent-exposed receptor surface shapes the orthosteric pocket and that NKR adopts a noncanonical active-state conformation with an interface for G protein binding, which is distinct from previously reported structures. Detailed comparisons with antagonist-bound NKR crystal structures reveal that insurmountable antagonists induce a distinct and long-lasting receptor conformation that sterically blocks SP binding. Together, our structures provide important structural insights into ligand and G protein promiscuity, the lack of basal signaling, and agonist- and antagonist-induced conformations in the neurokinin receptor family. 履歴 登録 2021年6月29日 - ヘッダ(付随情報) 公開 2021年12月15日 - マップ公開 2021年12月15日 - 更新 2021年12月15日 - 現状 2021年12月15日 処理サイト : PDBe / 状態 : 公開
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