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基本情報
登録情報 | データベース: EMDB / ID: EMD-8978 | |||||||||
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タイトル | Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor | |||||||||
![]() | Active, Gs-protein complexed, CGRP receptor | |||||||||
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![]() | class B G protein-coupled receptor / agonist-receptor-G protein ternary complex / calcitonin gene-related peptide receptor / receptor activity modifying protein 1 / active-state G protein-coupled receptor / signaling protein / phase plate / phase contrast | |||||||||
機能・相同性 | ![]() nervous system process involved in regulation of systemic arterial blood pressure / calcitonin gene-related peptide binding / cellular response to sucrose stimulus / adrenomedullin binding / CGRP receptor complex / positive regulation of protein glycosylation / adrenomedullin receptor activity / adrenomedullin receptor complex / adrenomedullin receptor signaling pathway / amylin receptor activity ...nervous system process involved in regulation of systemic arterial blood pressure / calcitonin gene-related peptide binding / cellular response to sucrose stimulus / adrenomedullin binding / CGRP receptor complex / positive regulation of protein glycosylation / adrenomedullin receptor activity / adrenomedullin receptor complex / adrenomedullin receptor signaling pathway / amylin receptor activity / calcitonin receptor activity / calcitonin gene-related peptide receptor signaling pathway / vascular associated smooth muscle cell proliferation / positive regulation of interleukin-1 alpha production / calcitonin gene-related peptide receptor activity / negative regulation of calcium ion transport into cytosol / positive regulation of macrophage differentiation / amylin receptor 1 signaling pathway / amylin receptor signaling pathway / Calcitonin-like ligand receptors / regulation of G protein-coupled receptor signaling pathway / G protein-coupled receptor internalization / vasculature development / endothelial cell proliferation / negative regulation of bone resorption / leukocyte cell-cell adhesion / negative regulation of osteoclast differentiation / PKA activation in glucagon signalling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hair follicle placode formation / developmental growth / regulation of cytosolic calcium ion concentration / D1 dopamine receptor binding / endothelial cell migration / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / cellular response to hormone stimulus / Hedgehog 'off' state / coreceptor activity / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / positive regulation of vascular associated smooth muscle cell proliferation / negative regulation of blood pressure / regulation of insulin secretion / cellular response to glucagon stimulus / adenylate cyclase activator activity / trans-Golgi network membrane / protein localization to plasma membrane / positive regulation of interleukin-8 production / intracellular protein transport / negative regulation of inflammatory response to antigenic stimulus / G protein-coupled receptor activity / hormone activity / bone development / receptor internalization / regulation of blood pressure / G-protein beta/gamma-subunit complex binding / platelet aggregation / cognition / 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 / adenylate cyclase-activating G protein-coupled 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 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / calcium ion transport / 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 / vasodilation / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / sensory perception of smell / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / protein transport / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste 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: 3.3 Å | |||||||||
![]() | Liang YL / Khoshouei M | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Cryo-EM structure of the active, G-protein complexed, human CGRP receptor. 著者: Yi-Lynn Liang / Maryam Khoshouei / Giuseppe Deganutti / Alisa Glukhova / Cassandra Koole / Thomas S Peat / Mazdak Radjainia / Jürgen M Plitzko / Wolfgang Baumeister / Laurence J Miller / ...著者: Yi-Lynn Liang / Maryam Khoshouei / Giuseppe Deganutti / Alisa Glukhova / Cassandra Koole / Thomas S Peat / Mazdak Radjainia / Jürgen M Plitzko / Wolfgang Baumeister / Laurence J Miller / Deborah L Hay / Arthur Christopoulos / Christopher A Reynolds / Denise Wootten / Patrick M Sexton / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() 要旨: Calcitonin gene-related peptide (CGRP) is a widely expressed neuropeptide that has a major role in sensory neurotransmission. The CGRP receptor is a heterodimer of the calcitonin receptor-like ...Calcitonin gene-related peptide (CGRP) is a widely expressed neuropeptide that has a major role in sensory neurotransmission. The CGRP receptor is a heterodimer of the calcitonin receptor-like receptor (CLR) class B G-protein-coupled receptor and a type 1 transmembrane domain protein, receptor activity-modifying protein 1 (RAMP1). Here we report the structure of the human CGRP receptor in complex with CGRP and the G-protein heterotrimer at 3.3 Å global resolution, determined by Volta phase-plate cryo-electron microscopy. The receptor activity-modifying protein transmembrane domain sits at the interface between transmembrane domains 3, 4 and 5 of CLR, and stabilizes CLR extracellular loop 2. RAMP1 makes only limited direct contact with CGRP, consistent with its function in allosteric modulation of CLR. Molecular dynamics simulations indicate that RAMP1 provides stability to the receptor complex, particularly in the positioning of the extracellular domain of CLR. This work provides insights into the control of G-protein-coupled receptor function. | |||||||||
履歴 |
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構造の表示
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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マップデータ | ![]() | 3.1 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 18.5 KB 18.5 KB | 表示 表示 | ![]() |
画像 | ![]() | 89.6 KB | ||
Filedesc metadata | ![]() | 6.9 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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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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注釈 | Active, Gs-protein complexed, CGRP receptor | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1.06 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
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試料の構成要素
-全体 : Complex of a full-length, active-state calcitonin gene-related pe...
全体 | 名称: Complex of a full-length, active-state calcitonin gene-related peptide receptor with calcitonin gene-related peptide ligand, heterotrimeric Gs protein and nanobody35 |
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要素 |
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-超分子 #1: Complex of a full-length, active-state calcitonin gene-related pe...
超分子 | 名称: Complex of a full-length, active-state calcitonin gene-related peptide receptor with calcitonin gene-related peptide ligand, heterotrimeric Gs protein and nanobody35 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: ![]() |
-分子 #1: Calcitonin gene-related peptide 1
分子 | 名称: Calcitonin gene-related peptide 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: 3.795354 KDa |
配列 | 文字列: ACDTATCVTH RLAGLLSRSG GVVKNNFVPT NVGSKAF(NH2) UniProtKB: Calcitonin gene-related peptide 1 |
-分子 #2: Nanobody 35
分子 | 名称: Nanobody 35 / 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: 15.140742 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSH HHHHHEPEA |
-分子 #3: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 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: 45.683434 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE ...文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE YQLIDCAQYF LDKIDVIKQA DYVPSDQDLL RCRVLTSGIF ETKFQVDKVN FHMFDVGAQR DERRKWIQCF ND VTAIIFV VASSSYNMVI REDNQTNRLQ AALKLFDSIW NNKWLRDTSV ILFLNKQDLL AEKVLAGKSK IEDYFPEFAR YTT PEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCA VDTENIRRVF NDCRDIIQRM HLRQYELL UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short |
-分子 #4: 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: 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: 38.534062 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-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: Calcitonin gene-related peptide type 1 receptor
分子 | 名称: Calcitonin gene-related peptide type 1 receptor / 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: ![]() |
分子量 | 理論値: 56.27452 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PAELEESPED SIQLGVTRNK IMTAQYECYQ KIMQDPIQQA EGVYCNRTWD GWLCWNDVA AGTESMQLCP DYFQDFDPSE KVTKICDQDG NWFRHPASNR TWTNYTQCNV NTHEKVKTAL NLFYLTIIGH G LSIASLLI ...文字列: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PAELEESPED SIQLGVTRNK IMTAQYECYQ KIMQDPIQQA EGVYCNRTWD GWLCWNDVA AGTESMQLCP DYFQDFDPSE KVTKICDQDG NWFRHPASNR TWTNYTQCNV NTHEKVKTAL NLFYLTIIGH G LSIASLLI SLGIFFYFKS LSCQRITLHK NLFFSFVCNS VVTIIHLTAV ANNQALVATN PVSCKVSQFI HLYLMGCNYF WM LCEGIYL HTLIVVAVFA EKQHLMWYYF LGWGFPLIPA CIHAIARSLY YNDNCWISSD THLLYIIHGP ICAALLVNLF FLL NIVRVL ITKLKVTHQA ESNLYMKAVR ATLILVPLLG IEFVLIPWRP EGKIAEEVYD YIMHILMHFQ GLLVSTIFCF FNGE VQAIL RRNWNQYKIQ FGNSFSNSEA LRSASYTVST ISDGPGYSHD CPSEHLNGKS IHDIENVLLK PENLYNPAGL EVLFQ GPHH HHHHHH UniProtKB: Calcitonin gene-related peptide type 1 receptor |
-分子 #7: Receptor activity-modifying protein 1
分子 | 名称: Receptor activity-modifying protein 1 / タイプ: protein_or_peptide / ID: 7 / 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: 17.066701 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDKHGSCQE ANYGALLREL CLTQFQVDME AVGETLWCDW GRTIRSYREL ADCTWHMAEK LGCFWPNAE VDRFFLAVHG RYFRSCPISG RAVRDPPGSI LYPFIVVPIT VTLLVTALVV WQSKRTEGIV UniProtKB: Receptor activity-modifying protein 1 |
-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: 7.4 |
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: COPPER / メッシュ: 200 |
凍結 | 凍結剤: NITROGEN / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV |
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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 SUMMIT (4k x 4k) 検出モード: COUNTING / 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 倍率(補正後): 47170 / 照射モード: OTHER / 撮影モード: BRIGHT FIELD |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: NONE |
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最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 407000 |
初期 角度割当 | タイプ: COMMON LINE |
最終 角度割当 | タイプ: PROJECTION MATCHING |