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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Human L-type voltage-gated calcium channel Cav1.2 (Class I) in the presence of pinaverium at 3.0 Angstrom resolution | |||||||||
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![]() | Cav1.2 / Channels / Calcium Ion-Selective / TRANSPORT PROTEIN / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() positive regulation of high voltage-gated calcium channel activity / voltage-gated calcium channel activity involved in AV node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / immune system development / positive regulation of adenylate cyclase activity / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / membrane depolarization during atrial cardiac muscle cell action potential / calcium ion transmembrane transport via high voltage-gated calcium channel / Phase 2 - plateau phase ...positive regulation of high voltage-gated calcium channel activity / voltage-gated calcium channel activity involved in AV node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / immune system development / positive regulation of adenylate cyclase activity / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / membrane depolarization during atrial cardiac muscle cell action potential / calcium ion transmembrane transport via high voltage-gated calcium channel / Phase 2 - plateau phase / membrane depolarization during AV node cell action potential / high voltage-gated calcium channel activity / membrane depolarization during bundle of His cell action potential / cardiac conduction / L-type voltage-gated calcium channel complex / positive regulation of muscle contraction / membrane depolarization during cardiac muscle cell action potential / cell communication by electrical coupling involved in cardiac conduction / regulation of ventricular cardiac muscle cell action potential / regulation of ventricular cardiac muscle cell membrane repolarization / NCAM1 interactions / camera-type eye development / cardiac muscle cell action potential involved in contraction / embryonic forelimb morphogenesis / calcium ion transport into cytosol / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / Mechanical load activates signaling by PIEZO1 and integrins in osteocytes / Phase 0 - rapid depolarisation / alpha-actinin binding / regulation of heart rate by cardiac conduction / regulation of calcium ion transport / calcium ion import across plasma membrane / neuronal dense core vesicle / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / voltage-gated calcium channel activity / presynaptic active zone membrane / sarcoplasmic reticulum / protein localization to plasma membrane / calcium channel regulator activity / Regulation of insulin secretion / postsynaptic density membrane / calcium ion transmembrane transport / GABA-ergic synapse / Z disc / cellular response to amyloid-beta / Adrenaline,noradrenaline inhibits insulin secretion / calcium ion transport / T cell receptor signaling pathway / heart development / positive regulation of cytosolic calcium ion concentration / perikaryon / chemical synaptic transmission / calmodulin binding / postsynaptic density / cilium / synapse / dendrite / extracellular exosome / nucleoplasm / metal ion binding / membrane / 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: 3.0 Å | |||||||||
![]() | Gao S / Yao X / Fan X / Yan N | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis for human Ca1.2 inhibition by multiple drugs and the neurotoxin calciseptine. 著者: Shuai Gao / Xia Yao / Jiaofeng Chen / Gaoxingyu Huang / Xiao Fan / Lingfeng Xue / Zhangqiang Li / Tong Wu / Yupeng Zheng / Jian Huang / Xueqin Jin / Yan Wang / Zhifei Wang / Yong Yu / Lei Liu ...著者: Shuai Gao / Xia Yao / Jiaofeng Chen / Gaoxingyu Huang / Xiao Fan / Lingfeng Xue / Zhangqiang Li / Tong Wu / Yupeng Zheng / Jian Huang / Xueqin Jin / Yan Wang / Zhifei Wang / Yong Yu / Lei Liu / Xiaojing Pan / Chen Song / Nieng Yan / ![]() ![]() 要旨: Ca1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Ca1.2, both in its apo form and in complex with several drugs, as well ...Ca1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Ca1.2, both in its apo form and in complex with several drugs, as well as the peptide neurotoxin calciseptine. Most structures, apo or bound to calciseptine, amlodipine, or a combination of amiodarone and sofosbuvir, exhibit a consistent inactivated conformation with a sealed gate, three up voltage-sensing domains (VSDs), and a down VSD. Calciseptine sits on the shoulder of the pore domain, away from the permeation path. In contrast, when pinaverium bromide, an antispasmodic drug, is inserted into a cavity reminiscent of the IFM-binding site in Na channels, a series of structural changes occur, including upward movement of VSD coupled with dilation of the selectivity filter and its surrounding segments in repeat III. Meanwhile, S4-5 merges with S5 to become a single helix, resulting in a widened but still non-conductive intracellular gate. | |||||||||
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マップデータ | ![]() | 79 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 23.6 KB 23.6 KB | 表示 表示 | ![]() |
画像 | ![]() | 44.4 KB | ||
Filedesc metadata | ![]() | 9.1 KB | ||
その他 | ![]() ![]() | 77.6 MB 77.6 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 963.9 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 963.5 KB | 表示 | |
XML形式データ | ![]() | 13 KB | 表示 | |
CIF形式データ | ![]() | 15.4 KB | 表示 | |
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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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ボクセルのサイズ | X=Y=Z: 1.114 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
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試料の構成要素
-全体 : Cav1.2
全体 | 名称: Cav1.2 |
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要素 |
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-超分子 #1: Cav1.2
超分子 | 名称: Cav1.2 / 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 #1: Voltage-dependent L-type calcium channel subunit alpha-1C
分子 | 名称: Voltage-dependent L-type calcium channel subunit alpha-1C 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: 246.85125 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MVNENTRMYI PEENHQGSNY GSPRPAHANM NANAAAGLAP EHIPTPGAAL SWQAAIDAAR QAKLMGSAGN ATISTVSSTQ RKRQQYGKP KKQGSTTATR PPRALLCLTL KNPIRRACIS IVEWKPFEII ILLTIFANCV ALAIYIPFPE DDSNATNSNL E RVEYLFLI ...文字列: MVNENTRMYI PEENHQGSNY GSPRPAHANM NANAAAGLAP EHIPTPGAAL SWQAAIDAAR QAKLMGSAGN ATISTVSSTQ RKRQQYGKP KKQGSTTATR PPRALLCLTL KNPIRRACIS IVEWKPFEII ILLTIFANCV ALAIYIPFPE DDSNATNSNL E RVEYLFLI IFTVEAFLKV IAYGLLFHPN AYLRNGWNLL DFIIVVVGLF SAILEQATKA DGANALGGKG AGFDVKALRA FR VLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFMGKMHKT CYNQEGIADV PAEDDPSPCA LET GHGRQC QNGTVCKPGW DGPKHGITNF DNFAFAMLTV FQCITMEGWT DVLYWVNDAV GRDWPWIYFV TLIIIGSFFV LNLV LGVLS GEFSKEREKA KARGDFQKLR EKQQLEEDLK GYLDWITQAE DIDPENEDEG MDEEKPRNMS MPTSETESVN TENVA GGDI EGENCGARLA HRISKSKFSR YWRRWNRFCR RKCRAAVKSN VFYWLVIFLV FLNTLTIASE HYNQPNWLTE VQDTAN KAL LALFTAEMLL KMYSLGLQAY FVSLFNRFDC FVVCGGILET ILVETKIMSP LGISVLRCVR LLRIFKITRY WNSLSNL VA SLLNSVRSIA SLLLLLFLFI IIFSLLGMQL FGGKFNFDEM QTRRSTFDNF PQSLLTVFQI LTGEDWNSVM YDGIMAYG G PSFPGMLVCI YFIILFICGN YILLNVFLAI AVDNLADAES LTSAQKEEEE EKERKKLART ASPEKKQELV EKPAVGESK EEKIELKSIT ADGESPPATK INMDDLQPNE NEDKSPYPNP ETTGEEDEEE PEMPVGPRPR PLSELHLKEK AVPMPEASAF FIFSSNNRF RLQCHRIVND TIFTNLILFF ILLSSISLAA EDPVQHTSFR NHILGNADYV FTSIFTLEII LKMTAYGAFL H KGSFCRNY FNILDLLVVS VSLISFGIQS SAINVVKILR VLRVLRPLRA INRAKGLKHV VQCVFVAIRT IGNIVIVTTL LQ FMFACIG VQLFKGKLYT CSDSSKQTEA ECKGNYITYK DGEVDHPIIQ PRSWENSKFD FDNVLAAMMA LFTVSTFEGW PEL LYRSID SHTEDKGPIY NYRVEISIFF IIYIIIIAFF MMNIFVGFVI VTFQEQGEQE YKNCELDKNQ RQCVEYALKA RPLR RYIPK NQHQYKVWYV VNSTYFEYLM FVLILLNTIC LAMQHYGQSC LFKIAMNILN MLFTGLFTVE MILKLIAFKP KGYFS DPWN VFDFLIVIGS IIDVILSETN HYFCDAWNTF DALIVVGSIV DIAITEVNPA EHTQCSPSMN AEENSRISIT FFRLFR VMR LVKLLSRGEG IRTLLWTFIK SFQALPYVAL LIVMLFFIYA VIGMQVFGKI ALNDTTEINR NNNFQTFPQA VLLLFRC AT GEAWQDIMLA CMPGKKCAPE SEPSNSTEGE TPCGSSFAVF YFISFYMLCA FLIINLFVAV IMDNFDYLTR DWSILGPH H LDEFKRIWAE YDPEAKGRIK HLDVVTLLRR IQPPLGFGKL CPHRVACKRL VSMNMPLNSD GTVMFNATLF ALVRTALRI KTEGNLEQAN EELRAIIKKI WKRTSMKLLD QVVPPAGDDE VTVGKFYATF LIQEYFRKFK KRKEQGLVGK PSQRNALSLQ AGLRTLHDI GPEIRRAISG DLTAEEELDK AMKEAVSAAS EDDIFRRAGG LFGNHVSYYQ SDGRSAFPQT FTTQRPLHIN K AGSSQGDT ESPSHEKLVD STFTPSSYSS TGSNANINNA NNTALGRLPR PAGYPSTVST VEGHGPPLSP AIRVQEVAWK LS SNRERHV PMCEDLELRR DSGSAGTQAH CLLLRKANPS RCHSRESQAA MAGQEETSQD ETYEVKMNHD TEACSEPSLL STE MLSYQD DENRQLTLPE EDKRDIRQSP KRGFLRSASL GRRASFHLEC LKRQKDRGGD ISQKTVLPLH LVHHQALAVA GLSP LLQRS HSPASFPRPF ATPPATPGSR GWPPQPVPTL RLEGVESSEK LNSSFPSIHC GSWAETTPGG GGSSAARRVR PVSLM VPSQ AGAPGRQFHG SASSLVEAVL ISEGLGQFAQ DPKFIEVTTQ ELADACDMTI EEMESAADNI LSGGAPQSPN GALLPF VNC RDAGQDRAGG EEDAGCVRAR GRPSEEELQD SRVYVSSL UniProtKB: Voltage-dependent L-type calcium channel subunit alpha-1C |
-分子 #2: Voltage-dependent calcium channel subunit alpha-2/delta-1
分子 | 名称: Voltage-dependent calcium channel subunit alpha-2/delta-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: 124.692469 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MAAGCLLALT LTLFQSLLIG PSSEEPFPSA VTIKSWVDKM QEDLVTLAKT ASGVNQLVDI YEKYQDLYTV EPNNARQLVE IAARDIEKL LSNRSKALVR LALEAEKVQA AHQWREDFAS NEVVYYNAKD DLDPEKNDSE PGSQRIKPVF IEDANFGRQI S YQHAAVHI ...文字列: MAAGCLLALT LTLFQSLLIG PSSEEPFPSA VTIKSWVDKM QEDLVTLAKT ASGVNQLVDI YEKYQDLYTV EPNNARQLVE IAARDIEKL LSNRSKALVR LALEAEKVQA AHQWREDFAS NEVVYYNAKD DLDPEKNDSE PGSQRIKPVF IEDANFGRQI S YQHAAVHI PTDIYEGSTI VLNELNWTSA LDEVFKKNRE EDPSLLWQVF GSATGLARYY PASPWVDNSR TPNKIDLYDV RR RPWYIQG AASPKDMLIL VDVSGSVSGL TLKLIRTSVS EMLETLSDDD FVNVASFNSN AQDVSCFQHL VQANVRNKKV LKD AVNNIT AKGITDYKKG FSFAFEQLLN YNVSRANCNK IIMLFTDGGE ERAQEIFNKY NKDKKVRVFT FSVGQHNYDR GPIQ WMACE NKGYYYEIPS IGAIRINTQE YLDVLGRPMV LAGDKAKQVQ WTNVYLDALE LGLVITGTLP VFNITGQFEN KTNLK NQLI LGVMGVDVSL EDIKRLTPRF TLCPNGYYFA IDPNGYVLLH PNLQPKPIGV GIPTINLRKR RPNIQNPKSQ EPVTLD FLD AELENDIKVE IRNKMIDGES GEKTFRTLVK SQDERYIDKG NRTYTWTPVN GTDYSLALVL PTYSFYYIKA KLEETIT QA RYSETLKPDN FEESGYTFIA PRDYCNDLKI SDNNTEFLLN FNEFIDRKTP NNPSCNADLI NRVLLDAGFT NELVQNYW S KQKNIKGVKA RFVVTDGGIT RVYPKEAGEN WQENPETYED SFYKRSLDND NYVFTAPYFN KSGPGAYESG IMVSKAVEI YIQGKLLKPA VVGIKIDVNS WIENFTKTSI RDPCAGPVCD CKRNSDVMDC VILDDGGFLL MANHDDYTNQ IGRFFGEIDP SLMRHLVNI SVYAFNKSYD YQSVCEPGAA PKQGAGHRSA YVPSVADILQ IGWWATAAAW SILQQFLLSL TFPRLLEAVE M EDDDFTAS LSKQSCITEQ TQYFFDNDSK SFSGVLDCGN CSRIFHGEKL MNTNLIFIMV ESKGTCPCDT RLLIQAEQTS DG PNPCDMV KQPRYRKGPD VCFDNNVLED YTDCGGVSGL NPSLWYIIGI QFLLLWLVSG STHRLL UniProtKB: Voltage-dependent calcium channel subunit alpha-2/delta-1 |
-分子 #3: Voltage-dependent L-type calcium channel subunit beta-3
分子 | 名称: Voltage-dependent L-type calcium channel subunit beta-3 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: 54.607852 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MYDDSYVPGF EDSEAGSADS YTSRPSLDSD VSLEEDRESA RREVESQAQQ QLERAKHKPV AFAVRTNVSY CGVLDEECPV QGSGVNFEA KDFLHIKEKY SNDWWIGRLV KEGGDIAFIP SPQRLESIRL KQEQKARRSG NPSSLSDIGN RRSPPPSLAK Q KQKQAEHV ...文字列: MYDDSYVPGF EDSEAGSADS YTSRPSLDSD VSLEEDRESA RREVESQAQQ QLERAKHKPV AFAVRTNVSY CGVLDEECPV QGSGVNFEA KDFLHIKEKY SNDWWIGRLV KEGGDIAFIP SPQRLESIRL KQEQKARRSG NPSSLSDIGN RRSPPPSLAK Q KQKQAEHV PPYDVVPSMR PVVLVGPSLK GYEVTDMMQK ALFDFLKHRF DGRISITRVT ADLSLAKRSV LNNPGKRTII ER SSARSSI AEVQSEIERI FELAKSLQLV VLDADTINHP AQLAKTSLAP IIVFVKVSSP KVLQRLIRSR GKSQMKHLTV QMM AYDKLV QCPPESFDVI LDENQLEDAC EHLAEYLEVY WRATHHPAPG PGLLGPPSAI PGLQNQQLLG ERGEEHSPLE RDSL MPSDE ASESSRQAWT GSSQRSSRHL EEDYADAYQD LYQPHRQHTS GLPSANGHDP QDRLLAQDSE HNHSDRNWQR NRPWP KDSY UniProtKB: Voltage-dependent L-type calcium channel subunit beta-3 |
-分子 #7: CALCIUM ION
分子 | 名称: CALCIUM ION / タイプ: ligand / ID: 7 / コピー数: 2 / 式: CA |
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分子量 | 理論値: 40.078 Da |
-分子 #8: 1,2-Distearoyl-sn-glycerophosphoethanolamine
分子 | 名称: 1,2-Distearoyl-sn-glycerophosphoethanolamine / タイプ: ligand / ID: 8 / コピー数: 1 / 式: 3PE |
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分子量 | 理論値: 748.065 Da |
Chemical component information | ![]() ChemComp-3PE: |
-分子 #9: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 9 / コピー数: 3 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-分子 #10: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 10 / コピー数: 3 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-分子 #11: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tr...
分子 | 名称: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate タイプ: ligand / ID: 11 / コピー数: 1 / 式: PT5 |
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分子量 | 理論値: 1.047088 KDa |
-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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凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 281 K |
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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) 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 | 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): 2.1 µm 最小 デフォーカス(公称値): 1.9000000000000001 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |