+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-22120 | |||||||||
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タイトル | Structure of human SMO-Gi complex with 24(S),25-EC | |||||||||
マップデータ | Structure of human SMO-Gi complex with 24(S),25-EC | |||||||||
試料 |
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キーワード | GPCR / MEMBRANE PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 ventral midline determination / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / regulation of heart morphogenesis / contact inhibition / negative regulation of hair follicle development / 9+0 non-motile cilium / central nervous system neuron differentiation / pancreas morphogenesis / regulation of somatic stem cell population maintenance / epithelial-mesenchymal cell signaling ...ventral midline determination / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / regulation of heart morphogenesis / contact inhibition / negative regulation of hair follicle development / 9+0 non-motile cilium / central nervous system neuron differentiation / pancreas morphogenesis / regulation of somatic stem cell population maintenance / epithelial-mesenchymal cell signaling / myoblast migration / atrial septum morphogenesis / spinal cord dorsal/ventral patterning / determination of left/right asymmetry in lateral mesoderm / Activation of SMO / left/right axis specification / ciliary tip / somite development / patched binding / forebrain morphogenesis / type B pancreatic cell development / positive regulation of branching involved in ureteric bud morphogenesis / thalamus development / positive regulation of organ growth / BBSome-mediated cargo-targeting to cilium / cellular response to cholesterol / dorsal/ventral neural tube patterning / smooth muscle tissue development / pattern specification process / cerebellar cortex morphogenesis / mammary gland epithelial cell differentiation / dentate gyrus development / dopaminergic neuron differentiation / oxysterol binding / commissural neuron axon guidance / positive regulation of multicellular organism growth / positive regulation of smoothened signaling pathway / Hedgehog 'off' state / Class B/2 (Secretin family receptors) / positive regulation of mesenchymal cell proliferation / cell fate specification / neural crest cell migration / cAMP-dependent protein kinase inhibitor activity / anterior/posterior pattern specification / ciliary membrane / hair follicle morphogenesis / midgut development / negative regulation of epithelial cell differentiation / smoothened signaling pathway / positive regulation of neuroblast proliferation / odontogenesis of dentin-containing tooth / heart looping / negative regulation of DNA binding / protein kinase A catalytic subunit binding / endoplasmic reticulum-Golgi intermediate compartment / neuroblast proliferation / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / vasculogenesis / regulation of cAMP-mediated signaling / skeletal muscle fiber development / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / homeostasis of number of cells within a tissue / protein sequestering activity / centriole / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / negative regulation of protein phosphorylation / positive regulation of epithelial cell proliferation / epithelial cell proliferation / central nervous system development / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / astrocyte activation / Hedgehog 'on' state / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / multicellular organism growth / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / cilium / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / cerebral cortex development / G beta:gamma signalling through CDC42 / response to peptide hormone / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 類似検索 - 分子機能 | |||||||||
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: 3.14 Å | |||||||||
データ登録者 | Qi X / Long T | |||||||||
引用 | ジャーナル: Nat Chem Biol / 年: 2020 タイトル: Sterols in an intramolecular channel of Smoothened mediate Hedgehog signaling. 著者: Xiaofeng Qi / Lucas Friedberg / Ryan De Bose-Boyd / Tao Long / Xiaochun Li / 要旨: Smoothened (SMO), a class Frizzled G protein-coupled receptor (class F GPCR), transduces the Hedgehog signal across the cell membrane. Sterols can bind to its extracellular cysteine-rich domain ...Smoothened (SMO), a class Frizzled G protein-coupled receptor (class F GPCR), transduces the Hedgehog signal across the cell membrane. Sterols can bind to its extracellular cysteine-rich domain (CRD) and to several sites in the seven transmembrane helices (7-TMs) of SMO. However, the mechanism by which sterols regulate SMO via multiple sites is unknown. Here we determined the structures of SMO-G complexes bound to the synthetic SMO agonist (SAG) and to 24(S),25-epoxycholesterol (24(S),25-EC). A novel sterol-binding site in the extracellular extension of TM6 was revealed to connect other sites in 7-TMs and CRD, forming an intramolecular sterol channel from the middle side of 7-TMs to CRD. Additional structures of two gain-of-function variants, SMO and SMO, showed that blocking the channel at its midpoints allows sterols to occupy the binding sites in 7-TMs, thereby activating SMO. These data indicate that sterol transport through the core of SMO is a major regulator of SMO-mediated signaling. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_22120.map.gz | 76.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-22120-v30.xml emd-22120.xml | 18.8 KB 18.8 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_22120.png | 39.7 KB | ||
マスクデータ | emd_22120_msk_1.map | 83.7 MB | マスクマップ | |
Filedesc metadata | emd-22120.cif.gz | 6.3 KB | ||
その他 | emd_22120_half_map_1.map.gz emd_22120_half_map_2.map.gz | 65.3 MB 65.3 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-22120 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22120 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_22120_validation.pdf.gz | 863 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_22120_full_validation.pdf.gz | 862.5 KB | 表示 | |
XML形式データ | emd_22120_validation.xml.gz | 12.6 KB | 表示 | |
CIF形式データ | emd_22120_validation.cif.gz | 14.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22120 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22120 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_22120.map.gz / 形式: CCP4 / 大きさ: 83.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Structure of human SMO-Gi complex with 24(S),25-EC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.832 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-マスク #1
ファイル | emd_22120_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Structure of human SMO-Gi complex with 24(S),25-EC
ファイル | emd_22120_half_map_1.map | ||||||||||||
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注釈 | Structure of human SMO-Gi complex with 24(S),25-EC | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Structure of human SMO-Gi complex with 24(S),25-EC
ファイル | emd_22120_half_map_2.map | ||||||||||||
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注釈 | Structure of human SMO-Gi complex with 24(S),25-EC | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : SMO-GI COMPLEX
全体 | 名称: SMO-GI COMPLEX |
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要素 |
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-超分子 #1: SMO-GI COMPLEX
超分子 | 名称: SMO-GI COMPLEX / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Smoothened homolog
分子 | 名称: Smoothened homolog / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 71.786438 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MAAARPARGP ELPLLGLLLL LLLGDPGRGA ASSGNATGPG PRSAGGSARR SAAVTGPPPP LSHCGRAAPC EPLRYNVCLG SVLPYGATS TLLAGDSDSQ EEAHGKLVLW SGLRNAPRCW AVIQPLLCAV YMPKCENDRV ELPSRTLCQA TRGPCAIVER E RGWPDFLR ...文字列: MAAARPARGP ELPLLGLLLL LLLGDPGRGA ASSGNATGPG PRSAGGSARR SAAVTGPPPP LSHCGRAAPC EPLRYNVCLG SVLPYGATS TLLAGDSDSQ EEAHGKLVLW SGLRNAPRCW AVIQPLLCAV YMPKCENDRV ELPSRTLCQA TRGPCAIVER E RGWPDFLR CTPDRFPEGC TNEVQNIKFN SSGQCEVPLV RTDNPKSWYE DVEGCGIQCQ NPLFTEAEHQ DMHSYIAAFG AV TGLCTLF TLATFVADWR NSNRYPAVIL FYVNACFFVG SIGWLAQFMD GARREIVCRA DGTMRLGEPT SNETLSCVII FVI VYYALM AGVVWFVVLT YAWHTSFKAL GTTYQPLSGK TSYFHLLTWS LPFVLTVAIL AVAQVDGDSV SGICFVGYKN YRYR AGFVL APIGLVLIVG GYFLIRGVMT LFSIKSNHPG LLSEKAASKI NETMLRLGIF GFLAFGFVLI TFSCHFYDFF NQAEW ERSF RDYVLCQANV TIGLPTKQPI PDCEIKNRPS LLVEKINLFA MFGTGIAMST WVWTKATLLI WRRTWCRLTG QSDDEP KRI KKSKMIAKAF SKRHELLQNP GQELSFSMHT VSHDGPVAGL AFDLNEPSAD VSSAWAQHVT KMVARRGAIL PQDISVT PV ATDYKDDDDK UniProtKB: Protein smoothened |
-分子 #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1 タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 40.415031 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGGQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 37.671102 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: PGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQD GKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY LSCCRFLDDN Q IVTSSGDT ...文字列: PGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQD GKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY LSCCRFLDDN Q IVTSSGDT TCALWDIETG QQTTTFTGHT GDVMSLSLAP DTRLFVSGAC DASAKLWDVR EGMCRQTFTG HESDINAICF FP NGNAFAT GSDDATCRLF DLRADQELMT YSHDNIICGI TSVSFSKSGR LLLAGYDDFN CNVWDALKAD RAGVLAGHDN RVS CLGVTD DGMAVATGSW DSFLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #5: scFv16
分子 | 名称: scFv16 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
分子量 | 理論値: 27.784896 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAAHHHHHH HH |
-分子 #6: 17-[3-(3,3-DIMETHYL-OXIRANYL)-1-METHYL-PROPYL]-10,13-DIMETHYL-2,3...
分子 | 名称: 17-[3-(3,3-DIMETHYL-OXIRANYL)-1-METHYL-PROPYL]-10,13-DIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1H-CYC LOPENTA[A]PHENANTHREN-3-OL タイプ: ligand / ID: 6 / コピー数: 2 / 式: CO1 |
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分子量 | 理論値: 400.637 Da |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: DARK FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: EMDB MAP |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.14 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 443107 |
初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |