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基本情報
登録情報 | ![]() | ||||||||||||||||||
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タイトル | Human adenylyl Cyclase 5 in complex with Gbg | ||||||||||||||||||
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![]() | Adenylyl cyclase / G-proteins / complex / SIGNALING PROTEIN | ||||||||||||||||||
機能・相同性 | ![]() Adenylate cyclase activating pathway / adenylate cyclase-inhibiting dopamine receptor signaling pathway / G protein-coupled adenosine receptor signaling pathway / adenylate cyclase / regulation of insulin secretion involved in cellular response to glucose stimulus / cAMP biosynthetic process / adenylate cyclase activity / PKA activation / PKA activation in glucagon signalling / neuromuscular process controlling balance ...Adenylate cyclase activating pathway / adenylate cyclase-inhibiting dopamine receptor signaling pathway / G protein-coupled adenosine receptor signaling pathway / adenylate cyclase / regulation of insulin secretion involved in cellular response to glucose stimulus / cAMP biosynthetic process / adenylate cyclase activity / PKA activation / PKA activation in glucagon signalling / neuromuscular process controlling balance / adenylate cyclase binding / Adenylate cyclase inhibitory pathway / Hedgehog 'off' state / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / FCGR3A-mediated IL10 synthesis / locomotory behavior / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / cilium / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / 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 / 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 / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / scaffold protein binding / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / intracellular signal transduction / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / ATP binding / membrane / metal ion binding / plasma membrane / cytosol / cytoplasm 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: 7.0 Å | ||||||||||||||||||
![]() | Yen YC / Tesmer JJG | ||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structure of adenylyl cyclase 5 in complex with Gβγ offers insights into ADCY5-related dyskinesia. 著者: Yu-Chen Yen / Yong Li / Chun-Liang Chen / Thomas Klose / Val J Watts / Carmen W Dessauer / John J G Tesmer / ![]() 要旨: The nine different membrane-anchored adenylyl cyclase isoforms (AC1-9) in mammals are stimulated by the heterotrimeric G protein, Gα, but their response to Gβγ regulation is isoform specific. In ...The nine different membrane-anchored adenylyl cyclase isoforms (AC1-9) in mammals are stimulated by the heterotrimeric G protein, Gα, but their response to Gβγ regulation is isoform specific. In the present study, we report cryo-electron microscope structures of ligand-free AC5 in complex with Gβγ and a dimeric form of AC5 that could be involved in its regulation. Gβγ binds to a coiled-coil domain that links the AC transmembrane region to its catalytic core as well as to a region (C) that is known to be a hub for isoform-specific regulation. We confirmed the Gβγ interaction with both purified proteins and cell-based assays. Gain-of-function mutations in AC5 associated with human familial dyskinesia are located at the interface of AC5 with Gβγ and show reduced conditional activation by Gβγ, emphasizing the importance of the observed interaction for motor function in humans. We propose a molecular mechanism wherein Gβγ either prevents dimerization of AC5 or allosterically modulates the coiled-coil domain, and hence the catalytic core. As our mechanistic understanding of how individual AC isoforms are uniquely regulated is limited, studies such as this may provide new avenues for isoform-specific drug development. | ||||||||||||||||||
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 | ![]() | 59.7 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 20.9 KB 20.9 KB | 表示 表示 | ![]() |
画像 | ![]() | 72.8 KB | ||
Filedesc metadata | ![]() | 6.9 KB | ||
その他 | ![]() ![]() | 59.4 MB 59.4 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8sl3MC ![]() 8sl4C M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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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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ボクセルのサイズ | X=Y=Z: 1.08 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: #1
ファイル | emd_40572_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: #2
ファイル | emd_40572_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 |
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試料の構成要素
-全体 : Human adenylyl cyclase 5 in complex with Gbg
全体 | 名称: Human adenylyl cyclase 5 in complex with Gbg |
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要素 |
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-超分子 #1: Human adenylyl cyclase 5 in complex with Gbg
超分子 | 名称: Human adenylyl cyclase 5 in complex with Gbg / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 180 KDa |
-分子 #1: Adenylate cyclase type 5
分子 | 名称: Adenylate cyclase type 5 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO / EC番号: adenylate cyclase |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 139.066312 KDa |
組換発現 | 生物種: Mammalia (両生類) |
配列 | 文字列: MSGSKSVSPP GYAAQKTAAP APRGGPEHRS AWGEADSRAN GYPHAPGGSA RGSTKKPGGA VTPQQQQRLA SRWRSDDDDD PPLSGDDPL AGGFGFSFRS KSAWQERGGD DCGRGSRRQR RGAASGGSTR APPAGGGGGS AAAAASAGGT EVRPRSVEVG L EERRGKGR ...文字列: MSGSKSVSPP GYAAQKTAAP APRGGPEHRS AWGEADSRAN GYPHAPGGSA RGSTKKPGGA VTPQQQQRLA SRWRSDDDDD PPLSGDDPL AGGFGFSFRS KSAWQERGGD DCGRGSRRQR RGAASGGSTR APPAGGGGGS AAAAASAGGT EVRPRSVEVG L EERRGKGR AADELEAGAV EGGEGSGDGG SSADSGSGAG PGAVLSLGAC CLALLQIFRS KKFPSDKLER LYQRYFFRLN QS SLTMLMA VLVLVCLVML AFHAARPPLQ LPYLAVLAAA VGVILIMAVL CNRAAFHQDH MGLACYALIA VVLAVQVVGL LLP QPRSAS EGIWWTVFFI YTIYTLLPVR MRAAVLSGVL LSALHLAIAL RTNAQDQFLL KQLVSNVLIF SCTNIVGVCT HYPA EVSQR QAFQETRECI QARLHSQREN QQQERLLLSV LPRHVAMEMK ADINAKQEDM MFHKIYIQKH DNVSILFADI EGFTS LASQ CTAQELVMTL NELFARFDKL AAENHCLRIK ILGDCYYCVS GLPEARADHA HCCVEMGMDM IEAISLVREV TGVNVN MRV GIHSGRVHCG VLGLRKWQFD VWSNDVTLAN HMEAGGKAGR IHITKATLNY LNGDYEVEPG CGGERNAYLK EHSIETF LI LRCTQKRKEE KAMIAKMNRQ RTNSIGHNPP HWGAERPFYN HLGGNQVSKE MKRMGFEDPK DKNAQESANP EDEVDEFL G RAIDARSIDR LRSEHVRKFL LTFREPDLEK KYSKQVDDRF GAYVACASLV FLFICFVQIT IVPHSIFMLS FYLTCSLLL TLVVFVSVIY SCVKLFPSPL QTLSRKIVRS KMNSTLVGVF TITLVFLAAF VNMFTCNSRD LLGCLAQEHN ISASQVNACH VAESAVNYS LGDEQGFCGS PWPNCNFPEY FTYSVLLSLL ACSVFLQISC IGKLVLMLAI ELIYVLIVEV PGVTLFDNAD L LVTANAID FFNNGTSQCP EHATKVALKV VTPIIISVFV LALYLHAQQV ESTARLDFLW KLQATEEKEE MEELQAYNRR LL HNILPKD VAAHFLARER RNDELYYQSC ECVAVMFASI ANFSEFYVEL EANNEGVECL RLLNEIIADF DEIISEDRFR QLE KIKTIG STYMAASGLN DSTYDKVGKT HIKALADFAM KLMDQMKYIN EHSFNNFQMK IGLNIGPVVA GVIGARKPQY DIWG NTVNV ASRMDSTGVP DRIQVTTDMY QVLAANTYQL ECRGVVKVKG KGEMMTYFLN GGPPLS UniProtKB: Adenylate cyclase type 5 |
-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: ![]() |
分子量 | 理論値: 37.41693 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-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: ![]() |
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 #4: GERAN-8-YL GERAN
分子 | 名称: GERAN-8-YL GERAN / タイプ: ligand / ID: 4 / コピー数: 1 / 式: GER |
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分子量 | 理論値: 274.484 Da |
Chemical component information | ![]() ChemComp-GER: |
-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
濃度 | 0.2 mg/mL | ||||||||||||||||||
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緩衝液 | pH: 7.4 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY | ||||||||||||||||||
凍結 | 凍結剤: ETHANE / 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 K3 (6k x 4k) / 平均電子線量: 53.8 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 100.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
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 |