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万見- EMDB-26179: Human Amylin2 Receptor in complex with Gs and human calcitonin peptide -
+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-26179 | ||||||||||||||||||||||||
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タイトル | Human Amylin2 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 / vascular associated smooth muscle cell development / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / adrenomedullin binding / basement membrane assembly / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 ...artery vasodilation involved in baroreceptor response to increased systemic arterial blood pressure / calcitonin receptor binding / vascular associated smooth muscle cell development / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / adrenomedullin binding / basement membrane assembly / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 / adrenomedullin receptor activity / adrenomedullin receptor complex / adrenomedullin receptor signaling pathway / 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 / positive regulation of vasculogenesis / bicellular tight junction assembly / regulation of G protein-coupled receptor signaling pathway / adherens junction assembly / feeding behavior / negative regulation of vascular permeability / negative regulation of ossification / negative regulation of bone resorption / 血管新生 / 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 / developmental growth / neuropeptide signaling pathway / intracellular transport / D1 dopamine receptor binding / cellular response to vascular endothelial growth factor stimulus / 脈管形成 / positive regulation of cAMP-mediated signaling / Hedgehog 'off' state / coreceptor activity / negative regulation of endothelial cell apoptotic process / positive regulation of calcium-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / クラスリン / response to glucocorticoid / cellular response to hormone stimulus / regulation of mRNA stability / regulation of cytosolic calcium ion concentration / activation of adenylate cyclase activity / adenylate cyclase activator activity / 着床 / hippocampal mossy fiber to CA3 synapse / 骨化 / osteoclast differentiation / cellular response to nerve growth factor stimulus / acrosomal vesicle / trans-Golgi network membrane / protein localization to plasma membrane / intracellular protein transport / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / 骨 / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / receptor internalization / adenylate cyclase-activating G protein-coupled receptor signaling pathway / terminal bouton / 繊毛 / hormone activity / 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 / 認識 / photoreceptor disc membrane / 血小板 / Adrenaline,noradrenaline inhibits insulin secretion / positive regulation of GTPase activity / Glucagon-type ligand receptors / 血圧 / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus 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: 3.3 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_26179.map.gz | 95.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-26179-v30.xml emd-26179.xml | 30 KB 30 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_26179_fsc.xml | 10.7 KB | 表示 | FSCデータファイル |
画像 | emd_26179.png | 28 KB | ||
マスクデータ | emd_26179_msk_1.map | 103 MB | マスクマップ | |
その他 | emd_26179_additional_1.map.gz emd_26179_additional_2.map.gz emd_26179_additional_3.map.gz emd_26179_half_map_1.map.gz emd_26179_half_map_2.map.gz | 81.1 MB 93.5 MB 91.8 MB 81.4 MB 81.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-26179 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26179 | HTTPS FTP |
-関連構造データ
関連構造データ | 7tyhMC 7tyfC 7tyiC 7tylC 7tynC 7tyoC 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_26179.map.gz / 形式: CCP4 / 大きさ: 103 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: 0.856 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_26179_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: unfiltered consensus map
ファイル | emd_26179_additional_1.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 |
-追加マップ: a post-processed map that focused on receptor region...
ファイル | emd_26179_additional_2.map | ||||||||||||
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注釈 | a post-processed map that focused on receptor region and was resampled to the consensus map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: an unfiltered map that focused on receptor region...
ファイル | emd_26179_additional_3.map | ||||||||||||
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注釈 | an unfiltered map that focused on receptor region and was resampled to the 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 for the consensus map refinement
ファイル | emd_26179_half_map_1.map | ||||||||||||
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注釈 | half map for the consensus map refinement | ||||||||||||
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 for the consensus map refinement
ファイル | emd_26179_half_map_2.map | ||||||||||||
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注釈 | half map for the consensus map refinement | ||||||||||||
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 : Human Amylin 2 Receptor in complex with Gs and human calcitonin p...
全体 | 名称: Human Amylin 2 Receptor in complex with Gs and human calcitonin peptide |
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要素 |
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-超分子 #1: Human Amylin 2 Receptor in complex with Gs and human calcitonin p...
超分子 | 名称: Human Amylin 2 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: all |
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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: Receptor activity-modifying protein 2
分子 | 名称: Receptor activity-modifying protein 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: Homo sapiens (ヒト) |
分子量 | 理論値: 17.839375 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 DDDKPLPTTG TPGSEGGTVK NYETAVQFCW NHYKDQMDPI EKDWCDWAMI SRPYSTLRDC LEHFAELFD LGFPNPLAER IIFETHQIHF ANCSLVQPTF SDPPEDVLLA MIIAPICLIP FLITLVVWRS KDSEAQA |
-分子 #6: Calcitonin
分子 | 名称: Calcitonin / 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: 3.42087 KDa |
配列 | 文字列: CGNLSTCMLG TYTQDFNKFH TFPQTAIGVG AP(NH2) |
-分子 #7: Calcitonin receptor
分子 | 名称: Calcitonin receptor / 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: 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 |
-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 | 4 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 GLACIOS |
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電子線 | 加速電圧: 200 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 FIELDBright-field microscopy / 最大 デフォーカス(公称値): 1.5 µm / 最小 デフォーカス(公称値): 0.5 µm |
撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 平均電子線量: 50.0 e/Å2 |