+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-35615 | ||||||||||||||||||||||||||||||||||||
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タイトル | Cryo-EM structure of the gamma-MSH-bound human melanocortin receptor 3 (MC3R)-Gs complex | ||||||||||||||||||||||||||||||||||||
マップデータ | |||||||||||||||||||||||||||||||||||||
試料 |
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キーワード | human melanocortin receptor 3 / G protein-coupled receptor / ligand recpgnition / membrane protein | ||||||||||||||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 homoiothermy / melanocyte-stimulating hormone receptor activity / melanocortin receptor activity / sodium ion homeostasis / regulation of feeding behavior / regulation of metabolic process / neuropeptide binding / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma ...homoiothermy / melanocyte-stimulating hormone receptor activity / melanocortin receptor activity / sodium ion homeostasis / regulation of feeding behavior / regulation of metabolic process / neuropeptide binding / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / locomotor rhythm / PKA activation in glucagon signalling / peptide hormone binding / hair follicle placode formation / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / developmental growth / D1 dopamine receptor binding / intracellular transport / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / renal water homeostasis / Hedgehog 'off' state / regulation of cAMP-mediated signaling / Transcriptional and post-translational regulation of MITF-M expression and activity / G protein-coupled serotonin receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / cellular response to forskolin / regulation of mitotic spindle organization / cellular response to glucagon stimulus / adenylate cyclase activator activity / regulation of insulin secretion / regulation of heart rate / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / viral budding from plasma membrane / trans-Golgi network membrane / Regulation of insulin secretion / G protein-coupled receptor binding / negative regulation of inflammatory response to antigenic stimulus / circadian regulation of gene expression / bone development / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 activity / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / platelet aggregation / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / response to peptide hormone / cognition / regulation of blood pressure / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / 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 類似検索 - 分子機能 | ||||||||||||||||||||||||||||||||||||
生物種 | Homo sapiens (ヒト) / Bos taurus (ウシ) / synthetic construct (人工物) | ||||||||||||||||||||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.86 Å | ||||||||||||||||||||||||||||||||||||
データ登録者 | Feng WB / Zhou QT / Chen XY / Dai AT / Cai XQ / Liu X / Zhao FH / Chen Y / Ye CY / Xu YN ...Feng WB / Zhou QT / Chen XY / Dai AT / Cai XQ / Liu X / Zhao FH / Chen Y / Ye CY / Xu YN / Cong ZT / Li H / Lin S | ||||||||||||||||||||||||||||||||||||
資金援助 | 中国, 11件
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引用 | ジャーナル: Cell Discov / 年: 2023 タイトル: Structural insights into ligand recognition and subtype selectivity of the human melanocortin-3 and melanocortin-5 receptors. 著者: Wenbo Feng / Qingtong Zhou / Xianyue Chen / Antao Dai / Xiaoqing Cai / Xiao Liu / Fenghui Zhao / Yan Chen / Chenyu Ye / Yingna Xu / Zhaotong Cong / Hao Li / Shi Lin / Dehua Yang / Ming-Wei Wang / 要旨: Members of the melanocortin receptor (MCR) family that recognize different melanocortin peptides mediate a broad spectrum of cellular processes including energy homeostasis, inflammation and skin ...Members of the melanocortin receptor (MCR) family that recognize different melanocortin peptides mediate a broad spectrum of cellular processes including energy homeostasis, inflammation and skin pigmentation through five MCR subtypes (MC1R-MC5R). The structural basis of subtype selectivity of the endogenous agonist γ-MSH and non-selectivity of agonist α-MSH remains elusive, as the two agonists are highly similar with a conserved HFRW motif. Here, we report three cryo-electron microscopy structures of MC3R-G in complex with γ-MSH and MC5R-G in the presence of α-MSH or a potent synthetic agonist PG-901. The structures reveal that α-MSH and γ-MSH adopt a "U-shape" conformation, penetrate into the wide-open orthosteric pocket and form massive common contacts with MCRs via the HFRW motif. The C-terminus of γ-MSH occupies an MC3R-specific complementary binding groove likely conferring subtype selectivity, whereas that of α-MSH distances itself from the receptor with neglectable contacts. PG-901 achieves the same potency as α-MSH with a shorter length by rebalancing the recognition site and mimicking the intra-peptide salt bridge in α-MSH by cyclization. Solid density confirmed the calcium ion binding in MC3R and MC5R, and the distinct modulation effects of divalent ions were demonstrated. Our results provide insights into ligand recognition and subtype selectivity among MCRs, and expand the knowledge of signal transduction among MCR family members. | ||||||||||||||||||||||||||||||||||||
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_35615.map.gz | 32.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-35615-v30.xml emd-35615.xml | 22.8 KB 22.8 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_35615_fsc.xml | 9.1 KB | 表示 | FSCデータファイル |
画像 | emd_35615.png | 70.9 KB | ||
その他 | emd_35615_half_map_1.map.gz emd_35615_half_map_2.map.gz | 59.4 MB 59.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-35615 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35615 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_35615_validation.pdf.gz | 700.4 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_35615_full_validation.pdf.gz | 699.9 KB | 表示 | |
XML形式データ | emd_35615_validation.xml.gz | 16.2 KB | 表示 | |
CIF形式データ | emd_35615_validation.cif.gz | 21.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35615 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35615 | 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_35615.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: 1.071 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_35615_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_35615_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 : Cryo-EM structure of gamma-MSH-bound human melanocortin receptor ...
全体 | 名称: Cryo-EM structure of gamma-MSH-bound human melanocortin receptor 3 in complex with G protein |
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要素 |
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-超分子 #1: Cryo-EM structure of gamma-MSH-bound human melanocortin receptor ...
超分子 | 名称: Cryo-EM structure of gamma-MSH-bound human melanocortin receptor 3 in complex with G protein タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine n...
分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 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: 41.879465 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RATHRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RATHRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTSGIFETK FQVDKVNFHM FDVGAQRDER RKWIQCFNDV TAIIFVVDSS DYNRLQEALN DF KSIWNNR WLRTISVILF LNKQDLLAEK VLAGKSKIED YFPEFARYTT PEDATPEPGE DPRVTRAKYF IRDEFLRIST ASG DGRHYC YPHFTCSVDT ENARRIFNDC RDIIQRMHLR QYELL UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(i) subunit alpha-1, ...UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short |
-分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,HiBiT
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,HiBiT 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: 40.226992 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...文字列: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD TTCALWDIET GQQTTTFTGH TGDVMSLSLA PDTRLFVSGA CDASAKLWDV REGMCRQTFT GHESDINAIC FF PNGNAFA TGSDDATCRL FDLRADQELM TYSHDNIICG ITSVSFSKSG RLLLAGYDDF NCNVWDALKA DRAGVLAGHD NRV SCLGVT DDGMAVATGS WDSFLKIWNG SSGGGGSGGG GSSGVSGWRL FKKIS UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: HA signal peptide,Melanocortin receptor 3,LgBiT subunit
分子 | 名称: HA signal peptide,Melanocortin receptor 3,LgBiT subunit 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: 56.351914 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MKTIIALSYI FCLVFANASC CLPSVQPTLP NGSEHLQAPF FSNQSSSAFC EQVFIKPEVF LSLGIVSLLE NILVILAVVR NGNLHSPMY FFLCSLAVAD MLVSVSNALE TIMIAIVHSD YLTFEDQFIQ HMDNIFDSMI CISLVASICN LLAIAVDRYV T IFYALRYH ...文字列: MKTIIALSYI FCLVFANASC CLPSVQPTLP NGSEHLQAPF FSNQSSSAFC EQVFIKPEVF LSLGIVSLLE NILVILAVVR NGNLHSPMY FFLCSLAVAD MLVSVSNALE TIMIAIVHSD YLTFEDQFIQ HMDNIFDSMI CISLVASICN LLAIAVDRYV T IFYALRYH SIMTVRKALT LIVAIWVCCG VCGVVFIVYS ESKMVIVCLI TMFFAMMLLM GTLYVHMFLF ARLHVKRIAA LP PADGVAP QQHSCMKGAV TITILLGVFI FCWAPFFLHL VLIITCPTNP YCICYTAHFN TYLVLIMCNS VIDPLIYAFR SLE LRNTFR EILCGCNGMN LGGSSGGGGS GGGGSSGVFT LEDFVGDWEQ TAAYNLDQVL EQGGVSSLLQ NLAVSVTPIQ RIVR SGENA LKIDIHVIIP YEGLSADQMA QIEEVFKVVY PVDDHHFKVI LPYGTLVIDG VTPNMLNYFG RPYEGIAVFD GKKIT VTGT LWNGNKIIDE RLITPDGSML FRVTINS UniProtKB: Hemagglutinin, Melanocortin receptor 3 |
-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: Bos taurus (ウシ) |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
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: gamma-melanocyte-stimulating hormone
分子 | 名称: gamma-melanocyte-stimulating hormone / 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: synthetic construct (人工物) |
分子量 | 理論値: 1.516747 KDa |
配列 | 文字列: YVMGHFRWDR F |
-分子 #6: Nanobody-35
分子 | 名称: Nanobody-35 / タイプ: protein_or_peptide / ID: 6 / 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: 17.352498 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MKYLLPTAAA GLLLLAAQPA MAQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGR FTISRDNAKN TLYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SHHHHHHEPE A |
-分子 #7: CALCIUM ION
分子 | 名称: CALCIUM ION / タイプ: ligand / ID: 7 / コピー数: 1 / 式: CA |
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分子量 | 理論値: 40.078 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: 7.4 |
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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: 80.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: OTHER |
電子光学系 | 照射モード: OTHER / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.2 µm / 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |