+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-33304 | |||||||||||||||||||||||||||
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タイトル | CryoEM structure of somatostatin receptor 4 (SSTR4) with Gi1 and J-2156 | |||||||||||||||||||||||||||
マップデータ | ||||||||||||||||||||||||||||
試料 |
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キーワード | G protein-coupled receptor / somatostatin receptor 2 / cryo-EM / STRUCTURAL PROTEIN | |||||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 somatostatin receptor activity / positive regulation of arachidonate secretion / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuropeptide binding / cellular response to glucocorticoid stimulus / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / neuropeptide signaling pathway / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway ...somatostatin receptor activity / positive regulation of arachidonate secretion / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuropeptide binding / cellular response to glucocorticoid stimulus / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / neuropeptide signaling pathway / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / G protein-coupled serotonin receptor binding / cellular response to forskolin / forebrain development / regulation of mitotic spindle organization / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / Peptide ligand-binding receptors / Regulation of insulin secretion / G protein-coupled receptor binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / 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 / 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 / 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 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GDP binding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / cell migration / signaling receptor complex adaptor activity / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / cell cortex / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / midbody / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / neuron projection / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / lysosomal membrane / cell division / GTPase activity / centrosome / synapse / GTP binding / protein-containing complex binding / nucleolus / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytosol / cytoplasm 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: 2.8 Å | |||||||||||||||||||||||||||
データ登録者 | Wenli Z / Shuo H / Na Q / Wenbo Z / Mengjie L / Dehua Y / Ming-Wei W / Wu B / Zhao Q | |||||||||||||||||||||||||||
資金援助 | 中国, 8件
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引用 | ジャーナル: Cell Res / 年: 2022 タイトル: Structural insights into ligand recognition and selectivity of somatostatin receptors. 著者: Wenli Zhao / Shuo Han / Na Qiu / Wenbo Feng / Mengjie Lu / Wenru Zhang / Mu Wang / Qingtong Zhou / Shutian Chen / Wei Xu / Juan Du / Xiaojing Chu / Cuiying Yi / Antao Dai / Liaoyuan Hu / ...著者: Wenli Zhao / Shuo Han / Na Qiu / Wenbo Feng / Mengjie Lu / Wenru Zhang / Mu Wang / Qingtong Zhou / Shutian Chen / Wei Xu / Juan Du / Xiaojing Chu / Cuiying Yi / Antao Dai / Liaoyuan Hu / Michelle Y Shen / Yaping Sun / Qing Zhang / Yingli Ma / Wenge Zhong / Dehua Yang / Ming-Wei Wang / Beili Wu / Qiang Zhao / 要旨: Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for ...Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for treating multiple tumors. Despite great progress made in therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity and conspicuous side-effects. Here, we report five structures of SSTR2 and SSTR4 in different states, including two crystal structures of SSTR2 in complex with a selective peptide antagonist and a non-peptide agonist, respectively, a cryo-electron microscopy (cryo-EM) structure of G-bound SSTR2 in the presence of the endogenous ligand SST-14, as well as two cryo-EM structures of G-bound SSTR4 in complex with SST-14 and a small-molecule agonist J-2156, respectively. By comparison of the SSTR structures in different states, molecular mechanisms of agonism and antagonism were illustrated. Together with computational and functional analyses, the key determinants responsible for ligand recognition and selectivity of different SSTR subtypes and multiform binding modes of peptide and non-peptide ligands were identified. Insights gained in this study will help uncover ligand selectivity of various SSTRs and accelerate the development of new molecules with better efficacy by targeting SSTRs. | |||||||||||||||||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_33304.map.gz | 59.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-33304-v30.xml emd-33304.xml | 21.6 KB 21.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_33304.png | 72.3 KB | ||
Filedesc metadata | emd-33304.cif.gz | 6.7 KB | ||
その他 | emd_33304_half_map_1.map.gz emd_33304_half_map_2.map.gz | 49.7 MB 49.7 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-33304 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33304 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_33304_validation.pdf.gz | 814.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_33304_full_validation.pdf.gz | 814.1 KB | 表示 | |
XML形式データ | emd_33304_validation.xml.gz | 12 KB | 表示 | |
CIF形式データ | emd_33304_validation.cif.gz | 14.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33304 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33304 | 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_33304.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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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: 1.045 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #2
ファイル | emd_33304_half_map_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: #1
ファイル | emd_33304_half_map_2.map | ||||||||||||
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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 : Complex structure of somatostatin receptor 4 (SSTR4) with Gi and ...
全体 | 名称: Complex structure of somatostatin receptor 4 (SSTR4) with Gi and J-2156 |
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要素 |
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-超分子 #1: Complex structure of somatostatin receptor 4 (SSTR4) with Gi and ...
超分子 | 名称: Complex structure of somatostatin receptor 4 (SSTR4) with Gi and J-2156 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: Somatostatin receptor type 4
分子 | 名称: Somatostatin receptor type 4 / 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: 40.667375 KDa |
組換発現 | 生物種: Insecta environmental sample (昆虫) |
配列 | 文字列: DYKDDDDGAP SAPSTLPPGG EEGLGTAWPS AANASSAPAE AEEAVAGPGD ARAAGMVAIQ CIYALVCLVG LVGNALVIFV ILRYAKMKT ATNIYLLNLA VADELFMLSV PFVASSAALR HWPFGSVLCR AVLSVDGLNM FTSVFCLTVL SVDRYVAVVH P LRAATYRR ...文字列: DYKDDDDGAP SAPSTLPPGG EEGLGTAWPS AANASSAPAE AEEAVAGPGD ARAAGMVAIQ CIYALVCLVG LVGNALVIFV ILRYAKMKT ATNIYLLNLA VADELFMLSV PFVASSAALR HWPFGSVLCR AVLSVDGLNM FTSVFCLTVL SVDRYVAVVH P LRAATYRR PSVAKLINLG VWLASLLVTL PIAIFADTRP ARGGQAVACN LQWPHPAWSA VFVVYTFLLG FLLPVLAIGL CY LLIVGKM RAVALRAGWQ QRRRSEKKIT RLVLMFVVVF VLCWMPFYVV QLLNLFVTSL DATVNHVSLI LSYANSCANP ILY GFLSDN FRRFFQRVLC LEFLEVLFQG PWSHPQFEKG GGSGGGSGGS AWSHPQFEK UniProtKB: Somatostatin receptor type 4 |
-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: 40.447141 KDa |
組換発現 | 生物種: Insecta environmental sample (昆虫) |
配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKCTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKCTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVTAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #3: single chain variable fragment of antibody
分子 | 名称: single chain variable fragment of antibody / 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: Mus musculus (ハツカネズミ) |
分子量 | 理論値: 31.549107 KDa |
組換発現 | 生物種: Insecta environmental sample (昆虫) |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDGAPSEPD VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS SGGGGSGGGG S GGGGSDIV ...文字列: MKTIIALSYI FCLVFADYKD DDDGAPSEPD VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS SGGGGSGGGG S GGGGSDIV MTQATSSVPV TPGESVSISC RSSKSLLHSN GNTYLYWFLQ RPGQSPQLLI YRMSNLASGV PDRFSGSGSG TA FTLTISR LEAEDVGVYY CMQHLEYPLT FGAGTKLELE FLEVLFQGPH HHHHH |
-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: Insecta environmental sample (昆虫) |
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: 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: 5 / 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: 38.744371 KDa |
組換発現 | 生物種: Insecta environmental sample (昆虫) |
配列 | 文字列: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI ...文字列: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DI NAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDALKADRAG VLA GHDNRV SCLGVTDDGM AVATGSWDSF LKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #6: (2~{S})-2-[[(2~{S})-4-azanyl-2-[(4-methylnaphthalen-1-yl)sulfonyl...
分子 | 名称: (2~{S})-2-[[(2~{S})-4-azanyl-2-[(4-methylnaphthalen-1-yl)sulfonylamino]butanoyl]amino]-3-phenyl-propanimidic acid タイプ: ligand / ID: 6 / コピー数: 1 / 式: I8B |
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分子量 | 理論値: 468.569 Da |
Chemical component information | ChemComp-I8B: |
-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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グリッド | 材質: NICKEL/TITANIUM |
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 BIOQUANTUM (6k x 4k) 平均電子線量: 70.0 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: BRIGHT FIELD 最大 デフォーカス(公称値): 2.3000000000000003 µm 最小 デフォーカス(公称値): 1.3 µm |
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: INSILICO MODEL |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 600908 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |