+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-27907 | |||||||||
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タイトル | Human L-type voltage-gated calcium channel Cav1.3 in the presence of Amiodarone at 3.1 Angstrom resolution | |||||||||
マップデータ | calcium channel | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 voltage-gated calcium channel activity involved SA node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / membrane depolarization during SA node cell action potential / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / regulation of potassium ion transmembrane transporter activity / positive regulation of high voltage-gated calcium channel activity / regulation of atrial cardiac muscle cell membrane repolarization / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential ...voltage-gated calcium channel activity involved SA node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / membrane depolarization during SA node cell action potential / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / regulation of potassium ion transmembrane transporter activity / positive regulation of high voltage-gated calcium channel activity / regulation of atrial cardiac muscle cell membrane repolarization / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during bundle of His cell action potential / positive regulation of adenylate cyclase activity / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / membrane depolarization during cardiac muscle cell action potential / positive regulation of calcium ion transport / cardiac muscle cell action potential involved in contraction / NCAM1 interactions / regulation of ventricular cardiac muscle cell membrane repolarization / calcium ion transport into cytosol / regulation of potassium ion transmembrane transport / calcium ion import / Sensory processing of sound by inner hair cells of the cochlea / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / ankyrin binding / neuromuscular junction development / calcium ion import across plasma membrane / 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 / sarcoplasmic reticulum / protein localization to plasma membrane / Regulation of insulin secretion / sensory perception of sound / calcium ion transmembrane transport / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / calcium channel activity / Z disc / Adrenaline,noradrenaline inhibits insulin secretion / cellular response to amyloid-beta / calcium ion transport / T cell receptor signaling pathway / chemical synaptic transmission / synapse / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol 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: 3.1 Å | |||||||||
データ登録者 | Gao S / Yao X / Yan N | |||||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Cell / 年: 2022 タイトル: Structural basis for the severe adverse interaction of sofosbuvir and amiodarone on L-type Ca channels. 著者: Xia Yao / Shuai Gao / Jixin Wang / Zhangqiang Li / Jian Huang / Yan Wang / Zhifei Wang / Jiaofeng Chen / Xiao Fan / Weipeng Wang / Xueqin Jin / Xiaojing Pan / Yong Yu / Armando Lagrutta / Nieng Yan / 要旨: Drug-drug interaction of the antiviral sofosbuvir and the antiarrhythmics amiodarone has been reported to cause fatal heartbeat slowing. Sofosbuvir and its analog, MNI-1, were reported to potentiate ...Drug-drug interaction of the antiviral sofosbuvir and the antiarrhythmics amiodarone has been reported to cause fatal heartbeat slowing. Sofosbuvir and its analog, MNI-1, were reported to potentiate the inhibition of cardiomyocyte calcium handling by amiodarone, which functions as a multi-channel antagonist, and implicate its inhibitory effect on L-type Ca channels, but the molecular mechanism has remained unclear. Here we present systematic cryo-EM structural analysis of Ca1.1 and Ca1.3 treated with amiodarone or sofosbuvir alone, or sofosbuvir/MNI-1 combined with amiodarone. Whereas amiodarone alone occupies the dihydropyridine binding site, sofosbuvir is not found in the channel when applied on its own. In the presence of amiodarone, sofosbuvir/MNI-1 is anchored in the central cavity of the pore domain through specific interaction with amiodarone and directly obstructs the ion permeation path. Our study reveals the molecular basis for the physical, pharmacodynamic interaction of two drugs on the scaffold of Ca channels. | |||||||||
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_27907.map.gz | 78.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-27907-v30.xml emd-27907.xml | 20.6 KB 20.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_27907.png | 138.2 KB | ||
その他 | emd_27907_half_map_1.map.gz emd_27907_half_map_2.map.gz | 65.4 MB 65.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-27907 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27907 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_27907_validation.pdf.gz | 818.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_27907_full_validation.pdf.gz | 818.2 KB | 表示 | |
XML形式データ | emd_27907_validation.xml.gz | 12.7 KB | 表示 | |
CIF形式データ | emd_27907_validation.cif.gz | 14.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27907 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27907 | 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_27907.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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注釈 | calcium channel | ||||||||||||||||||||||||||||||||||||
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: Half Map 1
ファイル | emd_27907_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_27907_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 : Cav1.3
全体 | 名称: Cav1.3 |
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要素 |
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-超分子 #1: Cav1.3
超分子 | 名称: Cav1.3 / タイプ: complex / ID: 1 / キメラ: Yes / 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-1D
分子 | 名称: Voltage-dependent L-type calcium channel subunit alpha-1D 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: 245.417734 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA RQAKAAQTMS TSAPPPVGSL SQRKRQQYA KSKKQGNSSN SRPARALFCL SLNNPIRRAC ISIVEWKPFD IFILLAIFAN CVALAIYIPF PEDDSNSTNH N LEKVEYAF ...文字列: MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA RQAKAAQTMS TSAPPPVGSL SQRKRQQYA KSKKQGNSSN SRPARALFCL SLNNPIRRAC ISIVEWKPFD IFILLAIFAN CVALAIYIPF PEDDSNSTNH N LEKVEYAF LIIFTVETFL KIIAYGLLLH PNAYVRNGWN LLDFVIVIVG LFSVILEQLT KETEGGNHSS GKSGGFDVKA LR AFRVLRP LRLVSGVPSL QVVLNSIIKA MVPLLHIALL VLFVIIIYAI IGLELFIGKM HKTCFFADSD IVAEEDPAPC AFS GNGRQC TANGTECRSG WVGPNGGITN FDNFAFAMLT VFQCITMEGW TDVLYWMNDA MGFELPWVYF VSLVIFGSFF VLNL VLGVL SGEFSKEREK AKARGDFQKL REKQQLEEDL KGYLDWITQA EDIDPENEEE GGEEGKRNTS MPTSETESVN TENVS GEGE NRGCCGSLCQ AISKSKLSRR WRRWNRFNRR RCRAAVKSVT FYWLVIVLVF LNTLTISSEH YNQPDWLTQI QDIANK VLL ALFTCEMLVK MYSLGLQAYF VSLFNRFDCF VVCGGITETI LVELEIMSPL GISVFRCVRL LRIFKVTRHW TSLSNLV AS LLNSMKSIAS LLLLLFLFII IFSLLGMQLF GGKFNFDETQ TKRSTFDNFP QALLTVFQIL TGEDWNAVMY DGIMAYGG P SSSGMIVCIY FIILFICGNY ILLNVFLAIA VDNLADAESL NTAQKEEAEE KERKKIARKE SLENKKNNKP EVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFT NLILVFIMLS SAALAAEDPI RSHSFRNTIL GYFDYAFTAI FTVEILLKMT TFGAFLHKGA FCRNYFNLLD M LVVGVSLV SFGIQSSAIS VVKILRVLRV LRPLRAINRA KGLKHVVQCV FVAIRTIGNI MIVTTLLQFM FACIGVQLFK GK FYRCTDE AKSNPEECRG LFILYKDGDV DSPVVRERIW QNSDFNFDNV LSAMMALFTV STFEGWPALL YKAIDSNGEN IGP IYNHRV EISIFFIIYI IIVAFFMMNI FVGFVIVTFQ EQGEKEYKNC ELDKNQRQCV EYALKARPLR RYIPKNPYQY KFWY VVNSS PFEYMMFVLI MLNTLCLAMQ HYEQSKMFND AMDILNMVFT GVFTVEMVLK VIAFKPKGYF SDAWNTFDSL IVIGS IIDV ALSEADPTES ENVPVPTATP GNSEESNRIS ITFFRLFRVM RLVKLLSRGE GIRTLLWTFI KSFQALPYVA LLIAML FFI YAVIGMQMFG KVAMRDNNQI NRNNNFQTFP QAVLLLFRCA TGEAWQEIML ACLPGKLCDP ESDYNPGEEY TCGSNFA IV YFISFYMLCA FLIINLFVAV IMDNFDYLTR DWSILGPHHL DEFKRIWSEY DPEAKGRIKH LDVVTLLRRI QPPLGFGK L CPHRVACKRL VAMNMPLNSD GTVMFNATLF ALVRTALKIK TEGNLEQANE ELRAVIKKIW KKTSMKLLDQ VVPPAGDDE VTVGKFYATF LIQDYFRKFK KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI GPEIRRAISC DLQDDEPEET KREEEDDVFK RNGALLGNH VNHVNSDRRD SLQQTNTTHR PLHVQRPSIP PASDTEKPLF PPAGNSVCHN HHNHNSIGKQ VPTSTNANLN N ANMSKAAH GKRPSIGNLE HVSENGHHSS HKHDREPQRR SSVKRTRYYE TYIRSDSGDE QLPTICREDP EIHGYFRDPH CL GEQEYFS SEECYEDDSS PTWSRQNYGY YSRYPGRNID SERPRGYHHP QGFLEDDDSP VCYDSRRSPR RRLLPPTPAS HRR SSFNFE CLRRQSSQEE VPSSPIFPHR TALPLHLMQQ QIMAVAGLDS SKAQKYSPSH STRSWATPPA TPPYRDWTPC YTPL IQVEQ SEALDQVNGS LPSLHRSSWY TDEPDISYRT FTPASLTVPS SFRNKNSDKQ RSADSLVEAV LISEGLGRYA RDPKF VSAT KHEIADACDL TIDEMESAAS TLLNGNVRPR ANGDVGPLSH RQDYELQDFG PGYSDEEPDP GRDEEDLADE MICITT L |
-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 |
-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 |
-分子 #7: (2-butyl-1-benzofuran-3-yl){4-[2-(diethylamino)ethoxy]-3,5-diiodo...
分子 | 名称: (2-butyl-1-benzofuran-3-yl){4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl}methanone タイプ: ligand / ID: 7 / コピー数: 1 / 式: BBI |
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分子量 | 理論値: 645.312 Da |
Chemical component information | ChemComp-BBI: |
-分子 #8: CALCIUM ION
分子 | 名称: CALCIUM ION / タイプ: ligand / ID: 8 / コピー数: 2 / 式: CA |
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分子量 | 理論値: 40.078 Da |
-分子 #9: 1,2-Distearoyl-sn-glycerophosphoethanolamine
分子 | 名称: 1,2-Distearoyl-sn-glycerophosphoethanolamine / タイプ: ligand / ID: 9 / 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 #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: 2 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-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
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 86836 |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |