登録情報 データベース : EMDB / ID : EMD-63327 ダウンロードとリンクタイトル Cryo-EM structure of the histamine H4 receptor-Gi protein complex (Overall) マップデータ 詳細 試料複合体 : Histamine H4 receptor-Gi protein complexタンパク質・ペプチド : Guanine nucleotide-binding protein G(i) subunit alpha-1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 : scFv16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 : Histamine H4 receptor,Genome polyproteinリガンド : HISTAMINEリガンド : water 詳細 キーワード GPCR / Class A GPCR / Histamine / G protein / Complex / MEMBRANE PROTEIN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
Histamine receptors / histamine receptor activity / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / neurotransmitter receptor activity / 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 ... Histamine receptors / histamine receptor activity / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / neurotransmitter receptor activity / 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 / Vasopressin regulates renal water homeostasis via Aquaporins / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / 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 / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (z) signalling events / Extra-nuclear estrogen signaling / photoreceptor outer segment membrane / G alpha (s) signalling events / G alpha (q) signalling events / spectrin 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 / alkylglycerophosphoethanolamine phosphodiesterase activity / regulation of MAPK cascade / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / photoreceptor outer segment / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / cardiac muscle cell apoptotic process / photoreceptor inner segment / cellular response to forskolin / regulation of mitotic spindle organization / bioluminescence / picornain 2A / generation of precursor metabolites and energy / symbiont-mediated suppression of host mRNA export from nucleus / Regulation of insulin secretion / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / positive regulation of cholesterol biosynthetic process / T=pseudo3 icosahedral viral capsid / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / host cell cytoplasmic vesicle membrane / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / GDP binding / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / sensory perception of taste / signaling receptor complex adaptor activity 類似検索 - 分子機能 Histamine H4 receptor / Green fluorescent protein, GFP / G-protein alpha subunit, group I / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent protein / Picornavirus coat protein / Poliovirus 3A protein-like / Poliovirus 3A protein like / Picornavirus 2B protein ... Histamine H4 receptor / Green fluorescent protein, GFP / G-protein alpha subunit, group I / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent protein / Picornavirus coat protein / Poliovirus 3A protein-like / Poliovirus 3A protein like / Picornavirus 2B protein / Poliovirus core protein 3a, soluble domain / Picornavirus 2B protein / Peptidase C3, picornavirus core protein 2A / Picornavirus core protein 2A / Picornavirus coat protein VP4 / Picornavirus coat protein (VP4) / Peptidase C3A/C3B, picornaviral / 3C cysteine protease (picornain 3C) / Picornavirales 3C/3C-like protease domain / Picornavirales 3C/3C-like protease domain profile. / Picornavirus capsid / picornavirus capsid protein / Helicase, superfamily 3, single-stranded RNA virus / Superfamily 3 helicase of positive ssRNA viruses domain profile. / Helicase, superfamily 3, single-stranded DNA/RNA virus / RNA helicase / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / Picornavirus/Calicivirus coat protein / Viral coat protein subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / 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 / RNA-directed RNA polymerase, C-terminal domain / Viral RNA-dependent RNA polymerase / Reverse transcriptase/Diguanylate cyclase domain / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / WD40/YVTN repeat-like-containing domain superfamily / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Genome polyprotein / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Histamine H4 receptor 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Rattus norvegicus (ドブネズミ) / Mus musculus (ハツカネズミ) / Bos taurus (ウシ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.84 Å 詳細 データ登録者Matsuzaki Y / Sano FK / Oshima HS / Akasaka H / Kobayashi K / Tanaka T / Itoh Y / Shihoya W / Kise Y / Kusakizako T / Nureki O 資金援助 日本, 1件 詳細 詳細を隠すOrganization Grant number 国 Japan Society for the Promotion of Science (JSPS) 日本
引用ジャーナル : Commun Biol / 年 : 2025タイトル : Structural insights into ligand recognition and G protein preferences across histamine receptors.著者 : Yuma Matsuzaki / Fumiya K Sano / Hidetaka S Oshima / Hiroaki Akasaka / Kazuhiro Kobayashi / Tatsuki Tanaka / Yuzuru Itoh / Wataru Shihoya / Yoshiaki Kise / Tsukasa Kusakizako / Asuka Inoue / Osamu Nureki / 要旨 : Histamine exerts critical physiological roles by activating four receptor subtypes, each exhibiting a specific G protein preference. Among these, the histamine H receptor (HR) modulates chemotaxis ... Histamine exerts critical physiological roles by activating four receptor subtypes, each exhibiting a specific G protein preference. Among these, the histamine H receptor (HR) modulates chemotaxis and interferon production through G protein activation, suggesting its therapeutic potential. Despite its physiological significance, the mechanisms underlying HR signalling and G protein preference across histamine receptors remain poorly understood. Here, we present the cryo-electron microscopy structure of the HR-G complex, revealing unique mechanisms of histamine recognition and receptor activation. We further solved the structures of the histamine H receptor (HR) bound to the non-canonical G proteins G and G. Through a combination of functional and computational analyses, we identified the intracellular loop 2 as a critical determinant of G protein preference in HR and HR. Collectively, our comprehensive study revealed the structural basis for distinct mechanisms of ligand recognition and receptor activation, offering a profound insight into G protein preference across receptor subtypes. 履歴 登録 2025年1月30日 - ヘッダ(付随情報) 公開 2025年6月11日 - マップ公開 2025年6月11日 - 更新 2025年7月23日 - 現状 2025年7月23日 処理サイト : PDBj / 状態 : 公開
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