+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-37472 | |||||||||
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タイトル | Human L-type voltage-gated calcium channel Cav1.2 at 2.9 Angstrom resolution | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | Cav1.2 / Channels / Calcium Ion-Selective / TRANSPORT PROTEIN / MEMBRANE PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 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 / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of high voltage-gated calcium channel activity / membrane depolarization during atrial cardiac muscle cell action potential / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / positive regulation of muscle contraction ...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 / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of high voltage-gated calcium channel activity / membrane depolarization during atrial cardiac muscle cell action potential / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / positive regulation of muscle contraction / membrane depolarization during AV node cell action potential / membrane depolarization during bundle of His cell action potential / positive regulation of adenylate cyclase activity / high voltage-gated calcium channel activity / cardiac conduction / L-type voltage-gated calcium channel complex / 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 / cardiac muscle cell action potential involved in contraction / camera-type eye development / NCAM1 interactions / regulation of ventricular cardiac muscle cell membrane repolarization / calcium ion transport into cytosol / embryonic forelimb morphogenesis / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / neuromuscular junction development / calcium ion import across plasma membrane / Phase 0 - rapid depolarisation / neuronal dense core vesicle / alpha-actinin binding / regulation of heart rate by cardiac conduction / regulation of calcium ion transport / calcium channel regulator activity / voltage-gated calcium channel activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / sarcoplasmic reticulum / protein localization to plasma membrane / Regulation of insulin secretion / calcium ion transmembrane transport / postsynaptic density membrane / Z disc / Adrenaline,noradrenaline inhibits insulin secretion / cellular response to amyloid-beta / calcium ion transport / heart development / T cell receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / chemical synaptic transmission / perikaryon / postsynaptic density / calmodulin binding / dendrite / synapse / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.9 Å | |||||||||
データ登録者 | Gao S / Yao X / Yan N | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Cell / 年: 2023 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. | |||||||||
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_37472.map.gz | 79.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-37472-v30.xml emd-37472.xml | 21.1 KB 21.1 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_37472.png | 37.4 KB | ||
Filedesc metadata | emd-37472.cif.gz | 8.5 KB | ||
その他 | emd_37472_half_map_1.map.gz emd_37472_half_map_2.map.gz | 77.6 MB 77.6 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-37472 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37472 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_37472_validation.pdf.gz | 1.2 MB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_37472_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | emd_37472_validation.xml.gz | 13 KB | 表示 | |
CIF形式データ | emd_37472_validation.cif.gz | 15.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37472 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37472 | HTTPS FTP |
-関連構造データ
-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_37472.map.gz / 形式: CCP4 / 大きさ: 83.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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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: 1.114 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
-ハーフマップ: #2
ファイル | emd_37472_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: #1
ファイル | emd_37472_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 |
-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: Homo sapiens (ヒト) |
-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: Homo sapiens (ヒト) |
分子量 | 理論値: 246.85125 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
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: Homo sapiens (ヒト) |
分子量 | 理論値: 124.692469 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
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: Homo sapiens (ヒト) |
分子量 | 理論値: 54.607852 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
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: 4 / 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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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-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 |
-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: 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): 2.1 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 |
-画像解析
初期モデル | モデルのタイプ: OTHER |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 74130 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |