+
データを開く
-
基本情報
登録情報 | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of HCA2-Gi complex with MK6892 | |||||||||
![]() | map | |||||||||
![]() |
| |||||||||
![]() | ![]() ![]() | |||||||||
機能・相同性 | ![]() Activation of the phototransduction cascade / Sensory perception of sweet, bitter, and umami (glutamate) taste / Olfactory Signaling Pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Prostacyclin signalling through prostacyclin receptor / G alpha (z) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 ...Activation of the phototransduction cascade / Sensory perception of sweet, bitter, and umami (glutamate) taste / Olfactory Signaling Pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Prostacyclin signalling through prostacyclin receptor / G alpha (z) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G beta:gamma signalling through BTK / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thromboxane signalling through TP receptor / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() ![]() ![]() | |||||||||
手法 | ![]() ![]() | |||||||||
![]() | Suzuki S / Nishikawa K / Suzuki H / Fujiyoshi Y | |||||||||
資金援助 | ![]()
| |||||||||
![]() | ![]() タイトル: Structural basis of hydroxycarboxylic acid receptor signaling mechanisms through ligand binding. 著者: Shota Suzuki / Kotaro Tanaka / Kouki Nishikawa / Hiroshi Suzuki / Atsunori Oshima / Yoshinori Fujiyoshi / ![]() 要旨: Hydroxycarboxylic acid receptors (HCA) are expressed in various tissues and immune cells. HCA2 and its agonist are thus important targets for treating inflammatory and metabolic disorders. Only ...Hydroxycarboxylic acid receptors (HCA) are expressed in various tissues and immune cells. HCA2 and its agonist are thus important targets for treating inflammatory and metabolic disorders. Only limited information is available, however, on the active-state binding of HCAs with agonists. Here, we present cryo-EM structures of human HCA2-Gi and HCA3-Gi signaling complexes binding with multiple compounds bound. Agonists were revealed to form a salt bridge with arginine, which is conserved in the HCA family, to activate these receptors. Extracellular regions of the receptors form a lid-like structure that covers the ligand-binding pocket. Although transmembrane (TM) 6 in HCAs undergoes dynamic conformational changes, ligands do not directly interact with amino acids in TM6, suggesting that indirect signaling induces a slight shift in TM6 to activate Gi proteins. Structural analyses of agonist-bound HCA2 and HCA3 together with mutagenesis and molecular dynamics simulation provide molecular insights into HCA ligand recognition and activation mechanisms. | |||||||||
履歴 |
|
-
構造の表示
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 | ![]() | 86 MB | ![]() | |
---|---|---|---|---|
ヘッダ (付随情報) | ![]() ![]() | 20.1 KB 20.1 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 9.5 KB | 表示 | ![]() |
画像 | ![]() | 42.1 KB | ||
マスクデータ | ![]() | 91.1 MB | ![]() | |
Filedesc metadata | ![]() | 7 KB | ||
その他 | ![]() ![]() | 84.7 MB 84.7 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
-
リンク
EMDBのページ | ![]() ![]() |
---|---|
「今月の分子」の関連する項目 |
-
マップ
ファイル | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | map | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.83 Å | ||||||||||||||||||||
密度 |
| ||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-マスク #1
ファイル | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: A
ファイル | emd_35443_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | A | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: B
ファイル | emd_35443_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | B | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-
試料の構成要素
-全体 : Multiprotein complex
全体 | 名称: Multiprotein complex![]() |
---|---|
要素 |
|
-超分子 #1: Multiprotein complex
超分子 | 名称: Multiprotein complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1, #3-#5, #2 |
---|---|
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 |
---|---|
由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 40.446047 KDa |
組換発現 | 生物種: ![]() ![]() ![]() |
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 FDVGAQRSER KKWIHCFEGV AAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY QEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #2: scFv16
分子 | 名称: scFv16 / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: synthetic construct (人工物) |
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 #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 |
---|---|
由来(天然) | 生物種: ![]() ![]() ![]() |
分子量 | 理論値: 41.772562 KDa |
組換発現 | 生物種: ![]() ![]() ![]() |
配列 | 文字列: MHHHHHHHHE NLYFQGSSEL DQLRQEAEQL KNQIRDARKA CADATLSQIT NNIDPVGRIQ MRTRRTLRGH LAKIYAMHWG TDSRLLVSA SQDGKLIIWD SYTTNKVHAI PLRSSWVMTC AYAPSGNYVA CGGLDNICSI YNLKTREGNV RVSRELAGHT G YLSCCRFL ...文字列: MHHHHHHHHE NLYFQGSSEL DQLRQEAEQL KNQIRDARKA CADATLSQIT NNIDPVGRIQ MRTRRTLRGH LAKIYAMHWG TDSRLLVSA SQDGKLIIWD SYTTNKVHAI PLRSSWVMTC AYAPSGNYVA CGGLDNICSI YNLKTREGNV RVSRELAGHT G YLSCCRFL DDNQIVTSSG DTTCALWDIE TGQQTTTFTG HTGDVMSLSL APDTRLFVSG ACDASAKLWD VREGMCRQTF TG HESDINA ICFFPNGNAF ATGSDDATCR LFDLRADQEL MTYSHDNIIC GITSVSFSKS GRLLLAGYDD FNCNVWDALK ADR AGVLAG HDNRVSCLGV TDDGMAVATG SWDSFLKIWN GGSGGGGSGG SSSGGVSGWR LFKKIS 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 |
---|---|
由来(天然) | 生物種: ![]() ![]() ![]() |
分子量 | 理論値: 7.729947 KDa |
組換発現 | 生物種: ![]() ![]() ![]() |
配列 | 文字列: ASNNTASIAQ ARKLVEQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASENPF REKKFFCAIL UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #5: Soluble cytochrome b562,Hydroxycarboxylic acid receptor 2
分子 | 名称: Soluble cytochrome b562,Hydroxycarboxylic acid receptor 2 タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 74.879688 KDa |
組換発現 | 生物種: ![]() ![]() ![]() |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDKADLEDN WETLNDNLKV IEKADNAAQV KDALTKMRAA ALDAQKATPP KLEDKSPDSP EMKDFRHGF DILVGQIDDA LKLANEGKVK EAQAAAEQLK TTRNAYIQKY LNRHHLQDHF LEIDKKNCCV FRDDFIVKVL P PVLGLEFI ...文字列: MKTIIALSYI FCLVFADYKD DDDKADLEDN WETLNDNLKV IEKADNAAQV KDALTKMRAA ALDAQKATPP KLEDKSPDSP EMKDFRHGF DILVGQIDDA LKLANEGKVK EAQAAAEQLK TTRNAYIQKY LNRHHLQDHF LEIDKKNCCV FRDDFIVKVL P PVLGLEFI FGLLGNGLAL WIFCFHLKSW KSSRIFLFNL AVADFLLIIC LPFLMDNYVR RWDWKFGDIP CRLMLFMLAM NR QGSIIFL TVVAVDRYFR VVHPHHALNK ISNRTAAIIS CLLWGITIGL TVHLLKKKMP IQNGGANLCS SFSICHTFQW HEA MFLLEF FLPLGIILFC SARIIWSLRQ RQMDRHAKIK RAITFIMVVA IVFVICFLPS VVVRIRIFWL LHTSGTQNCE VYRS VDLAF FITLSFTYMN SMLDPVVYYF SSPSFPNFFS TLINRCLQRK MTGEPDNNRS TSVELTGDPN KTRGAPEALM ANSGE PWSP SYLGPTSPEN LYFQGSVFTL EDFVGDWEQT AAYNLDQVLE QGGVSSLLQN LAVSVTPIQR IVRSGENALK IDIHVI IPY EGLSADQMAQ IEEVFKVVYP VDDHHFKVIL PYGTLVIDGV TPNMLNYFGR PYEGIAVFDG KKITVTGTLW NGNKIID ER LITPDGSMLF RVTINS UniProtKB: Soluble cytochrome b562, Hydroxycarboxylic acid receptor 2 |
-分子 #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 6 / コピー数: 1 / 式: NAG |
---|---|
分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-分子 #7: 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: 7 / コピー数: 1 / 式: FI7 |
---|---|
分子量 | 理論値: 386.402 Da |
Chemical component information | ![]() ChemComp-FI7: |
-実験情報
-構造解析
手法 | ![]() |
---|---|
![]() | ![]() |
試料の集合状態 | particle |
-
試料調製
濃度 | 15 mg/mL |
---|---|
緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 298 K / 装置: FEI VITROBOT MARK IV |
詳細 | This sample was monodisperse |
-
電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
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![]() 最小 デフォーカス(公称値): 0.7000000000000001 µm |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 49.0 e/Å2 |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |