登録情報 データベース : PDB / ID : 6u1n 構造の表示 ダウンロードとリンクタイトル GPCR-Beta arrestin structure in lipid bilayer 要素Beta-arrestin-1 Fab30 heavy chain Fab30 light chain Muscarinic acetylcholine receptor M2, Vasopressin V2 receptor chimera 詳細キーワード SIGNALING PROTEIN/IMMUNE SYSTEM / Arrestin / GPCR / complex / signaling / SIGNALING PROTEIN-IMMUNE SYSTEM 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
V2 vasopressin receptor binding / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / sensory perception of touch / renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / G alpha (s) signalling events / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity ... V2 vasopressin receptor binding / alpha-1A adrenergic receptor binding / follicle-stimulating hormone receptor binding / sensory perception of touch / renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / G alpha (s) signalling events / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / alpha-1B adrenergic receptor binding / follicle-stimulating hormone signaling pathway / protein phosphorylated amino acid binding / angiotensin receptor binding / Lysosome Vesicle Biogenesis / AP-2 adaptor complex binding / Muscarinic acetylcholine receptors / symmetric synapse / Golgi Associated Vesicle Biogenesis / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / MAP2K and MAPK activation / Ub-specific processing proteases / G protein-coupled acetylcholine receptor activity / hemostasis / positive regulation of systemic arterial blood pressure / cholinergic synapse / telencephalon development / regulation of smooth muscle contraction / positive regulation of smooth muscle cell apoptotic process / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / negative regulation of interleukin-8 production / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / clathrin adaptor activity / regulation of G protein-coupled receptor signaling pathway / G protein-coupled serotonin receptor activity / arrestin family protein binding / G protein-coupled receptor internalization / response to morphine / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of intracellular signal transduction / mitogen-activated protein kinase kinase binding / regulation of heart contraction / positive regulation of Rho protein signal transduction / clathrin binding / negative regulation of Notch signaling pathway / stress fiber assembly / pseudopodium / positive regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of interleukin-6 production / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / positive regulation of receptor internalization / phototransduction / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / endocytic vesicle / asymmetric synapse / immunoglobulin complex, circulating / activation of adenylate cyclase activity / immunoglobulin receptor binding / axon terminus / clathrin-coated pit / positive regulation of vasoconstriction / cellular response to hormone stimulus / negative regulation of protein ubiquitination / visual perception / presynaptic modulation of chemical synaptic transmission / GTPase activator activity / complement activation, classical pathway / negative regulation of protein phosphorylation / positive regulation of protein ubiquitination / response to cytokine / G protein-coupled receptor binding / antigen binding / nuclear estrogen receptor binding / phosphoprotein binding / insulin-like growth factor receptor binding / peptide binding / clathrin-coated endocytic vesicle membrane / response to virus / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / negative regulation of ERK1 and ERK2 cascade / Vasopressin regulates renal water homeostasis via Aquaporins / endocytosis / protein transport / Cargo recognition for clathrin-mediated endocytosis / positive regulation of peptidyl-serine phosphorylation / Clathrin-mediated endocytosis / nervous system development / presynaptic membrane / antibacterial humoral response / G alpha (i) signalling events / cytoplasmic vesicle / ubiquitin-dependent protein catabolic process / G alpha (s) signalling events / chemical synaptic transmission / basolateral plasma membrane / postsynaptic membrane / regulation of apoptotic process / proteasome-mediated ubiquitin-dependent protein catabolic process 類似検索 - 分子機能 Muscarinic acetylcholine receptor M2 / Vasopressin V2 receptor / Vasopressin receptor / Muscarinic acetylcholine receptor family / Arrestin, conserved site / Arrestins signature. / Arrestin / Arrestin, N-terminal / Arrestin-like, N-terminal / Arrestin C-terminal-like domain ... Muscarinic acetylcholine receptor M2 / Vasopressin V2 receptor / Vasopressin receptor / Muscarinic acetylcholine receptor family / Arrestin, conserved site / Arrestins signature. / Arrestin / Arrestin, N-terminal / Arrestin-like, N-terminal / Arrestin C-terminal-like domain / Arrestin (or S-antigen), N-terminal domain / Arrestin (or S-antigen), C-terminal domain / Arrestin (or S-antigen), C-terminal domain / Arrestin-like, C-terminal / : / : / Serpentine type 7TM GPCR chemoreceptor Srsx / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / 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) / Immunoglobulin E-set / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulin subtype / Immunoglobulin / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold 類似検索 - ドメイン・相同性 Chem-2CU / Muscarinic acetylcholine receptor M2 / Beta-arrestin-1 / Vasopressin V2 receptor / Ig-like domain-containing protein / Epididymis luminal protein 214 類似検索 - 構成要素生物種 Homo sapiens (ヒト)Rattus norvegicus (ドブネズミ)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 Staus, D.P. / Hu, H. / Robertson, M.J. / Kleinhenz, A.L.W. / Wingler, L.M. / Capel, W.D. / Latorraca, N.R. / Lefkowitz, R.J. / Skiniotis, G. 資金援助 米国, 2件 詳細 詳細を隠す組織 認可番号 国 National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) HL16037 米国 National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) NS092695 米国
引用ジャーナル : Nature / 年 : 2020タイトル : Structure of the M2 muscarinic receptor-β-arrestin complex in a lipid nanodisc.著者 : Dean P Staus / Hongli Hu / Michael J Robertson / Alissa L W Kleinhenz / Laura M Wingler / William D Capel / Naomi R Latorraca / Robert J Lefkowitz / Georgios Skiniotis / 要旨 : After activation by an agonist, G-protein-coupled receptors (GPCRs) recruit β-arrestin, which desensitizes heterotrimeric G-protein signalling and promotes receptor endocytosis. Additionally, β- ... After activation by an agonist, G-protein-coupled receptors (GPCRs) recruit β-arrestin, which desensitizes heterotrimeric G-protein signalling and promotes receptor endocytosis. Additionally, β-arrestin directly regulates many cell signalling pathways that can induce cellular responses distinct from that of G proteins. In contrast to G proteins, for which there are many high-resolution structures in complex with GPCRs, the molecular mechanisms underlying the interaction of β-arrestin with GPCRs are much less understood. Here we present a cryo-electron microscopy structure of β-arrestin 1 (βarr1) in complex with M2 muscarinic receptor (M2R) reconstituted in lipid nanodiscs. The M2R-βarr1 complex displays a multimodal network of flexible interactions, including binding of the N domain of βarr1 to phosphorylated receptor residues and insertion of the finger loop of βarr1 into the M2R seven-transmembrane bundle, which adopts a conformation similar to that in the M2R-heterotrimeric G protein complex. Moreover, the cryo-electron microscopy map reveals that the C-edge of βarr1 engages the lipid bilayer. Through atomistic simulations and biophysical, biochemical and cellular assays, we show that the C-edge is critical for stable complex formation, βarr1 recruitment, receptor internalization, and desensitization of G-protein activation. Taken together, these data suggest that the cooperative interactions of β-arrestin with both the receptor and the phospholipid bilayer contribute to its functional versatility. 履歴 登録 2019年8月16日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2020年2月26日 Provider : repository / タイプ : Initial release改定 1.1 2020年3月4日 Group : Database references / カテゴリ : citation / Item : _citation.pdbx_database_id_PubMed / _citation.title改定 1.2 2020年3月25日 Group : Database references / カテゴリ : citationItem : _citation.journal_volume / _citation.page_first / _citation.page_last
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