登録情報 データベース : EMDB / ID : EMD-27062 ダウンロードとリンクタイトル Cryo-EM structure of the unliganded mSMO-PGS2 in a lipidic environment マップデータ 詳細 試料複合体 : mSMO-PGS2タンパク質・ペプチド : Smoothened homolog, GlgA glycogen synthase chimeraリガンド : CHOLESTEROL 詳細 キーワード G-protein coupled receptor / Smoothened / unliganded state / lipid system / 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
regulation of localization / BBSome-mediated cargo-targeting to cilium / ventral midline determination / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / response to inositol / Activation of SMO / regulation of heart morphogenesis / contact inhibition / negative regulation of hair follicle development / 9+0 non-motile cilium ... regulation of localization / BBSome-mediated cargo-targeting to cilium / ventral midline determination / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / response to inositol / Activation of SMO / regulation of heart morphogenesis / contact inhibition / negative regulation of hair follicle development / 9+0 non-motile cilium / pancreas morphogenesis / regulation of somatic stem cell population maintenance / epithelial-mesenchymal cell signaling / myoblast migration / atrial septum morphogenesis / Hedgehog 'on' state / spinal cord dorsal/ventral patterning / determination of left/right asymmetry in lateral mesoderm / midgut development / cell development / alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity / left/right axis specification / Hedgehog 'off' state / negative regulation of DNA binding / patched binding / forebrain morphogenesis / type B pancreatic cell development / somite development / positive regulation of organ growth / dorsal/ventral neural tube patterning / smooth muscle tissue development / cerebellar cortex morphogenesis / positive regulation of branching involved in ureteric bud morphogenesis / cellular response to cholesterol / pattern specification process / mammary gland epithelial cell differentiation / dentate gyrus development / dopaminergic neuron differentiation / oxysterol binding / thalamus development / positive regulation of multicellular organism growth / positive regulation of smoothened signaling pathway / dorsal/ventral pattern formation / digestive tract development / determination of left/right symmetry / cell fate specification / central nervous system neuron differentiation / cAMP-dependent protein kinase inhibitor activity / neural crest cell migration / anterior/posterior pattern specification / positive regulation of mesenchymal cell proliferation / ciliary membrane / hair follicle morphogenesis / smoothened signaling pathway / negative regulation of epithelial cell differentiation / positive regulation of neuroblast proliferation / heart looping / protein kinase A catalytic subunit binding / endoplasmic reticulum-Golgi intermediate compartment / odontogenesis of dentin-containing tooth / negative regulation of protein phosphorylation / developmental growth / neuroblast proliferation / hair follicle development / protein localization to nucleus / embryonic organ development / heart morphogenesis / vasculogenesis / skeletal muscle fiber development / epithelial cell differentiation / centriole / homeostasis of number of cells within a tissue / astrocyte activation / ossification / protein sequestering activity / central nervous system development / epithelial cell proliferation / positive regulation of epithelial cell proliferation / G protein-coupled receptor activity / cerebral cortex development / caveola / positive regulation of protein import into nucleus / multicellular organism growth / endocytic vesicle membrane / protein import into nucleus / osteoblast differentiation / late endosome / regulation of gene expression / gene expression / in utero embryonic development / cell population proliferation / protein stabilization / cilium / positive regulation of cell migration / negative regulation of gene expression / negative regulation of DNA-templated transcription / positive regulation of cell population proliferation / apoptotic process / positive regulation of gene expression / negative regulation of apoptotic process 類似検索 - 分子機能 Smoothened, transmembrane domain / Smoothened, cysteine-rich domain / Glycosyl transferases group 1 / Bacterial/plant glycogen synthase / Starch synthase, catalytic domain / Starch synthase catalytic domain / Frizzled/Smoothened, transmembrane domain / Frizzled/Smoothened family membrane region / Frizzled/Smoothened family membrane region / Frizzled/secreted frizzled-related protein ... Smoothened, transmembrane domain / Smoothened, cysteine-rich domain / Glycosyl transferases group 1 / Bacterial/plant glycogen synthase / Starch synthase, catalytic domain / Starch synthase catalytic domain / Frizzled/Smoothened, transmembrane domain / Frizzled/Smoothened family membrane region / Frizzled/Smoothened family membrane region / Frizzled/secreted frizzled-related protein / Frizzled / Frizzled domain / Frizzled cysteine-rich domain superfamily / Fz domain / Frizzled (fz) domain profile. / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. 類似検索 - ドメイン・相同性生物種 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 : 3.7 Å 詳細 データ登録者Zhang K / Wu H / Hoppe N / Manglik A / Cheng Y 資金援助 フランス, 米国, 3件 詳細 詳細を隠すOrganization Grant number 国 Human Frontier Science Program (HFSP) LT000471/2017-L フランス National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) GM140847 米国 National Institutes of Health/National Center for Advancing Translational Sciences (NIH/NCATS) TR003384 米国
引用ジャーナル : Nat Commun / 年 : 2022タイトル : Fusion protein strategies for cryo-EM study of G protein-coupled receptors.著者 : Kaihua Zhang / Hao Wu / Nicholas Hoppe / Aashish Manglik / Yifan Cheng / 要旨 : Single particle cryogenic-electron microscopy (cryo-EM) is used extensively to determine structures of activated G protein-coupled receptors (GPCRs) in complex with G proteins or arrestins. However, ... Single particle cryogenic-electron microscopy (cryo-EM) is used extensively to determine structures of activated G protein-coupled receptors (GPCRs) in complex with G proteins or arrestins. However, applying it to GPCRs without signaling proteins remains challenging because most receptors lack structural features in their soluble domains to facilitate image alignment. In GPCR crystallography, inserting a fusion protein between transmembrane helices 5 and 6 is a highly successful strategy for crystallization. Although a similar strategy has the potential to broadly facilitate cryo-EM structure determination of GPCRs alone without signaling protein, the critical determinants that make this approach successful are not yet clear. Here, we address this shortcoming by exploring different fusion protein designs, which lead to structures of antagonist bound A adenosine receptor at 3.4 Å resolution and unliganded Smoothened at 3.7 Å resolution. The fusion strategies explored here are likely applicable to cryo-EM interrogation of other GPCRs and small integral membrane proteins. 履歴 登録 2022年5月22日 - ヘッダ(付随情報) 公開 2022年8月3日 - マップ公開 2022年8月3日 - 更新 2024年10月9日 - 現状 2024年10月9日 処理サイト : RCSB / 状態 : 公開
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