+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-26190 | ||||||||||||||||||||||||
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タイトル | Calcitonin receptor in complex with Gs and human calcitonin peptide | ||||||||||||||||||||||||
マップデータ | post processed consensus map | ||||||||||||||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 artery vasodilation involved in baroreceptor response to increased systemic arterial blood pressure / calcitonin receptor binding / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 / amylin receptor activity / calcitonin receptor activity / calcitonin gene-related peptide receptor activity ...artery vasodilation involved in baroreceptor response to increased systemic arterial blood pressure / calcitonin receptor binding / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 / amylin receptor activity / calcitonin receptor activity / calcitonin gene-related peptide receptor activity / amylin receptor signaling pathway / positive regulation of adenylate cyclase activity / Calcitonin-like ligand receptors / feeding behavior / negative regulation of ossification / negative regulation of bone resorption / negative regulation of smooth muscle contraction / response to pain / activation of protein kinase activity / neuronal dense core vesicle / positive regulation of protein kinase A signaling / monocyte chemotaxis / detection of temperature stimulus involved in sensory perception of pain / PKA activation in glucagon signalling / response to amyloid-beta / hair follicle placode formation / smooth muscle contraction / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / intracellular transport / D1 dopamine receptor binding / neuropeptide signaling pathway / Hedgehog 'off' state / positive regulation of calcium-mediated signaling / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / response to glucocorticoid / regulation of mRNA stability / regulation of cytosolic calcium ion concentration / activation of adenylate cyclase activity / adenylate cyclase activator activity / embryo implantation / hippocampal mossy fiber to CA3 synapse / ossification / osteoclast differentiation / cellular response to nerve growth factor stimulus / acrosomal vesicle / trans-Golgi network membrane / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / bone development / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / hormone activity / terminal bouton / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / cilium / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye 類似検索 - 分子機能 | ||||||||||||||||||||||||
生物種 | Homo sapiens (ヒト) / Lama glama (ラマ) | ||||||||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.7 Å | ||||||||||||||||||||||||
データ登録者 | Cao J / Belousoff MJ / Johnson RM / Wootten DL / Sexton PM | ||||||||||||||||||||||||
資金援助 | オーストラリア, 日本, 7件
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引用 | ジャーナル: Science / 年: 2022 タイトル: A structural basis for amylin receptor phenotype. 著者: Jianjun Cao / Matthew J Belousoff / Yi-Lynn Liang / Rachel M Johnson / Tracy M Josephs / Madeleine M Fletcher / Arthur Christopoulos / Debbie L Hay / Radostin Danev / Denise Wootten / Patrick M Sexton / 要旨: Amylin receptors (AMYRs) are heterodimers of the calcitonin (CT) receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs), AMYR, AMYR, and AMYR. Selective AMYR agonists and dual ...Amylin receptors (AMYRs) are heterodimers of the calcitonin (CT) receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs), AMYR, AMYR, and AMYR. Selective AMYR agonists and dual AMYR/CTR agonists are being developed as obesity treatments; however, the molecular basis for peptide binding and selectivity is unknown. We determined the structure and dynamics of active AMYRs with amylin, AMYR with salmon CT (sCT), AMYR with sCT or human CT (hCT), and CTR with amylin, sCT, or hCT. The conformation of amylin-bound complexes was similar for all AMYRs, constrained by the RAMP, and an ordered midpeptide motif that we call the bypass motif. The CT-bound AMYR complexes were distinct, overlapping the CT-bound CTR complexes. Our findings indicate that activation of AMYRs by CT-based peptides is distinct from their activation by amylin-based peptides. This has important implications for the development of AMYR therapeutics. | ||||||||||||||||||||||||
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_26190.map.gz | 59.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-26190-v30.xml emd-26190.xml | 27.4 KB 27.4 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_26190_fsc.xml | 9.1 KB | 表示 | FSCデータファイル |
画像 | emd_26190.png | 31.8 KB | ||
マスクデータ | emd_26190_msk_1.map | 64 MB | マスクマップ | |
その他 | emd_26190_additional_1.map.gz emd_26190_additional_2.map.gz emd_26190_half_map_1.map.gz emd_26190_half_map_2.map.gz | 1.8 MB 49.8 MB 49.9 MB 49.9 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-26190 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26190 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_26190_validation.pdf.gz | 884.2 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_26190_full_validation.pdf.gz | 883.8 KB | 表示 | |
XML形式データ | emd_26190_validation.xml.gz | 16 KB | 表示 | |
CIF形式データ | emd_26190_validation.cif.gz | 21.1 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26190 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26190 | HTTPS FTP |
-関連構造データ
関連構造データ | 7tyoMC 7tyfC 7tyhC 7tyiC 7tylC 7tynC 7tywC 7tyxC 7tyyC 7tzfC C: 同じ文献を引用 (文献) M: このマップから作成された原子モデル |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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_26190.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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注釈 | post processed consensus map | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.91406 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 | emd_26190_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-追加マップ: focussed map for receptor
ファイル | emd_26190_additional_1.map | ||||||||||||
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注釈 | focussed map for receptor | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: unfiltered consensus map
ファイル | emd_26190_additional_2.map | ||||||||||||
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注釈 | unfiltered consensus map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half map 1
ファイル | emd_26190_half_map_1.map | ||||||||||||
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注釈 | half map 1 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half map 2
ファイル | emd_26190_half_map_2.map | ||||||||||||
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注釈 | half map 2 | ||||||||||||
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 : Calcitonin receptor in complex with Gs and human calcitonin peptide
全体 | 名称: Calcitonin receptor in complex with Gs and human calcitonin peptide |
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要素 |
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-超分子 #1: Calcitonin receptor in complex with Gs and human calcitonin peptide
超分子 | 名称: Calcitonin receptor in complex with Gs and human calcitonin peptide タイプ: complex / キメラ: Yes / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6 |
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-分子 #1: 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: 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: 45.699434 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
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 HYCYPHFTCS VDTENIRRVF NDCRDIIQRM HLRQYELL |
-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: Homo sapiens (ヒト) |
分子量 | 理論値: 38.534062 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
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 |
-分子 #3: 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: 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: 7.861143 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-分子 #4: Nanobody 35
分子 | 名称: Nanobody 35 / 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: Lama glama (ラマ) |
分子量 | 理論値: 15.140742 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSH HHHHHEPEA |
-分子 #5: Calcitonin
分子 | 名称: Calcitonin / 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: 3.42087 KDa |
配列 | 文字列: CGNLSTCMLG TYTQDFNKFH TFPQTAIGVG AP(NH2) |
-分子 #6: Calcitonin receptor
分子 | 名称: Calcitonin 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: Homo sapiens (ヒト) |
分子量 | 理論値: 58.469594 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PAAFSNQTYP TIEPKPFLYV VGRKKMMDAQ YKCYDRMQQL PAYQGEGPYC NRTWDGWLC WDDTPAGVLS YQFCPDYFPD FDPSEKVTKY CDEKGVWFKH PENNRTWSNY TMCNAFTPEK LKNAYVLYYL A IVGHSLSI ...文字列: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PAAFSNQTYP TIEPKPFLYV VGRKKMMDAQ YKCYDRMQQL PAYQGEGPYC NRTWDGWLC WDDTPAGVLS YQFCPDYFPD FDPSEKVTKY CDEKGVWFKH PENNRTWSNY TMCNAFTPEK LKNAYVLYYL A IVGHSLSI FTLVISLGIF VFFRSLGCQR VTLHKNMFLT YILNSMIIII HLVEVVPNGE LVRRDPVSCK ILHFFHQYMM AC NYFWMLC EGIYLHTLIV VAVFTEKQRL RWYYLLGWGF PLVPTTIHAI TRAVYFNDNC WLSVETHLLY IIHGPVMAAL VVN FFFLLN IVRVLVTKMR ETHEAESHMY LKAVKATMIL VPLLGIQFVV FPWRPSNKML GKIYDYVMHS LIHFQGFFVA TIYC FCNNE VQTTVKRQWA QFKIQWNQRW GRRPSNRSAR AAAAAAEAGD IPIYICHQEL RNEPANNQGE ESAEIIPLNI IEQES SAPA GLEVLFQGPH HHHHHHH |
-分子 #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 7 / コピー数: 1 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-分子 #8: CHOLESTEROL HEMISUCCINATE
分子 | 名称: CHOLESTEROL HEMISUCCINATE / タイプ: ligand / ID: 8 / コピー数: 2 / 式: Y01 |
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分子量 | 理論値: 486.726 Da |
Chemical component information | ChemComp-Y01: |
-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
濃度 | 7 mg/mL |
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緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | TFS 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: 70.6 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): 2.0 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |