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基本情報
登録情報 | ![]() | ||||||||||||||||||
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タイトル | Cryo-EM Structure of Human Niacin Receptor HCA2-Gi protein complex | ||||||||||||||||||
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![]() | Niacin receptor / hydroxycarboxylic acid receptor 2 / HCA2 / Gi complex / MEMBRANE PROTEIN | ||||||||||||||||||
機能・相同性 | ![]() nicotinic acid receptor activity / Hydroxycarboxylic acid-binding receptors / neutrophil apoptotic process / positive regulation of neutrophil apoptotic process / Class A/1 (Rhodopsin-like receptors) / positive regulation of adiponectin secretion / negative regulation of lipid catabolic process / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration ...nicotinic acid receptor activity / Hydroxycarboxylic acid-binding receptors / neutrophil apoptotic process / positive regulation of neutrophil apoptotic process / Class A/1 (Rhodopsin-like receptors) / positive regulation of adiponectin secretion / negative regulation of lipid catabolic process / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / Adenylate cyclase inhibitory pathway / 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 / cellular response to forskolin / regulation of mitotic spindle organization / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / centriolar satellite / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / 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 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / GDP binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / ADP signalling through P2Y purinoceptor 1 / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / cell junction / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / G protein activity / GTPase binding / Ca2+ pathway / midbody / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / cell cortex / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / 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 / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / ciliary basal body / G protein-coupled receptor signaling pathway / lysosomal membrane / cell division / GTPase activity / synapse / centrosome / GTP binding / protein-containing complex binding / nucleolus / magnesium ion binding / Golgi apparatus / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane 類似検索 - 分子機能 | ||||||||||||||||||
生物種 | ![]() | ||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.1 Å | ||||||||||||||||||
![]() | Yang Y / Kang HJ / Gao RG / Wang JJ / Han GW / DiBerto JF / Wu LJ / Tong JH / Qu L / Wu YR ...Yang Y / Kang HJ / Gao RG / Wang JJ / Han GW / DiBerto JF / Wu LJ / Tong JH / Qu L / Wu YR / Pileski R / Li XM / Zhang XC / Zhao SW / Kenakin T / Wang Q / Stevens RC / Peng W / Roth BL / Rao ZH / Liu ZJ | ||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into the human niacin receptor HCA2-G signalling complex. 著者: Yang Yang / Hye Jin Kang / Ruogu Gao / Jingjing Wang / Gye Won Han / Jeffrey F DiBerto / Lijie Wu / Jiahui Tong / Lu Qu / Yiran Wu / Ryan Pileski / Xuemei Li / Xuejun Cai Zhang / Suwen Zhao / ...著者: Yang Yang / Hye Jin Kang / Ruogu Gao / Jingjing Wang / Gye Won Han / Jeffrey F DiBerto / Lijie Wu / Jiahui Tong / Lu Qu / Yiran Wu / Ryan Pileski / Xuemei Li / Xuejun Cai Zhang / Suwen Zhao / Terry Kenakin / Quan Wang / Raymond C Stevens / Wei Peng / Bryan L Roth / Zihe Rao / Zhi-Jie Liu / ![]() ![]() ![]() 要旨: The hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. ...The hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. Extensive efforts have been made to identify HCA2 targeting lipid lowering agents with fewer adverse effects, despite little being known about the molecular basis of HCA2 mediated signalling. Here, we report the cryo-electron microscopy structure of the HCA2-G signalling complex with the potent agonist MK-6892, along with crystal structures of HCA2 in inactive state. These structures, together with comprehensive pharmacological analysis, reveal the ligand binding mode and activation and signalling mechanisms of HCA2. This study elucidates the structural determinants essential for HCA2 mediated signalling and provides insights into ligand discovery for HCA2 and related receptors. | ||||||||||||||||||
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構造の表示
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マップデータ | ![]() | 59.7 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 25.8 KB 25.8 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 9.3 KB | 表示 | ![]() |
画像 | ![]() | 49 KB | ||
マスクデータ | ![]() | 64 MB | ![]() | |
Filedesc metadata | ![]() | 7.6 KB | ||
その他 | ![]() ![]() | 59.4 MB 59.4 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 794.1 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 793.8 KB | 表示 | |
XML形式データ | ![]() | 16.3 KB | 表示 | |
CIF形式データ | ![]() | 20.9 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 7xk2MC ![]() 7zl9C ![]() 7zlyC M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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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: 1.04 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
-マスク #1
ファイル | ![]() | ||||||||||||
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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: #2
ファイル | emd_33241_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_33241_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 |
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試料の構成要素
-全体 : Niacin Receptor HCA2-Gi complex
全体 | 名称: Niacin Receptor HCA2-Gi complex |
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要素 |
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-超分子 #1: Niacin Receptor HCA2-Gi complex
超分子 | 名称: Niacin Receptor HCA2-Gi complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2, #4-#5 |
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由来(天然) | 生物種: ![]() |
-分子 #1: 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: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 40.55916 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: GSMGCTLSAE DKAAVERSKM IDRNLREDGE KAAREVKLLL LGAGESGKST IVKQMKIIHE AGYSEEECKQ YKAVVYSNTI QSIIAIIRA MGRLKIDFGD SARADDARQL FVLAGAAEEG FMTAELAGVI KRLWKDSGVQ ACFNRSREYQ LNDSAAYYLN D LDRIAQPN ...文字列: GSMGCTLSAE DKAAVERSKM IDRNLREDGE KAAREVKLLL LGAGESGKST IVKQMKIIHE AGYSEEECKQ YKAVVYSNTI QSIIAIIRA MGRLKIDFGD SARADDARQL FVLAGAAEEG FMTAELAGVI KRLWKDSGVQ ACFNRSREYQ LNDSAAYYLN D LDRIAQPN YIPTQQDVLR TRVKTTGIVE THFTFKDLHF KMFDVGGQRS ERKKWIHCFE GVTAIIFCVA LSDYDLVLAE DE EMNRMHE SMKLFDSICN NKWFTDTSII LFLNKKDLFE EKIKKSPLTI CYPEYAGSNT YEEAAAYIQC QFEDLNKRKD TKE IYTHFT CATDTKNVQF VFDAVTDVII KNNLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #2: 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: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 37.41693 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: Hydroxycarboxylic acid receptor 2
分子 | 名称: Hydroxycarboxylic acid receptor 2 / 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: ![]() |
分子量 | 理論値: 38.010254 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MNRHHLQDHF LEIDKKNCCV FRDDFIVKVL PPVLGLEFIF GLLGNGLALW IFCFHLKSWK SSRIFLFNLA VADFLLIICL PFLMDNYVR RWDWKFGDIP CRLMLFMLAM NRQGSIIFLT VVAVDRYFRV VHPHHALNKI SNRTAAIISC LLWGITIGLT V HLLKKKMP ...文字列: MNRHHLQDHF LEIDKKNCCV FRDDFIVKVL PPVLGLEFIF GLLGNGLALW IFCFHLKSWK SSRIFLFNLA VADFLLIICL PFLMDNYVR RWDWKFGDIP CRLMLFMLAM NRQGSIIFLT VVAVDRYFRV VHPHHALNKI SNRTAAIISC LLWGITIGLT V HLLKKKMP IQNGGANLCS SFSICHTFQW HEAMFLLEFF LPLGIILFCS ARIIWSLRQR QMDRHAKIKR AITFIMVVAI VF VICFLPS VVVRIRIFWL LHTSGTQNCE VYRSVDLAFF ITLSFTYMNS MLDPVVYYFS SPSFPNFFST LINRCLQRKM TGE PDNNR UniProtKB: Hydroxycarboxylic acid receptor 2 |
-分子 #4: scFv16
分子 | 名称: scFv16 / 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: ![]() |
分子量 | 理論値: 26.466486 KDa |
組換発現 | 生物種: ![]() |
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 K |
-分子 #5: 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: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: ![]() |
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 #6: 2-[[2,2-dimethyl-3-[3-(5-oxidanylpyridin-2-yl)-1,2,4-oxadiazol-5-...
分子 | 名称: 2-[[2,2-dimethyl-3-[3-(5-oxidanylpyridin-2-yl)-1,2,4-oxadiazol-5-yl]propanoyl]amino]cyclohexene-1-carboxylic acid タイプ: ligand / ID: 6 / コピー数: 1 / 式: FI7 |
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分子量 | 理論値: 386.402 Da |
Chemical component information | ![]() ChemComp-FI7: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
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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 K2 QUANTUM (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
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): 2.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |