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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Structure of human R-type voltage-gated CaV2.3-alpha2/delta1-beta1 channel complex in the ligand-free (apo) state | |||||||||
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機能・相同性 | ![]() regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of high voltage-gated calcium channel activity / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / positive regulation of muscle contraction / membrane depolarization during bundle of His cell action potential / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / cardiac muscle cell action potential involved in contraction ...regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of high voltage-gated calcium channel activity / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / positive regulation of muscle contraction / membrane depolarization during bundle of His cell action potential / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / cardiac muscle cell action potential involved in contraction / voltage-gated monoatomic cation channel activity / NCAM1 interactions / regulation of ventricular cardiac muscle cell membrane repolarization / calcium ion transport into cytosol / 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 / regulation of heart rate by cardiac conduction / regulation of calcium ion transport / voltage-gated calcium channel activity / T-tubule / sarcoplasmic reticulum / Regulation of insulin secretion / calcium ion transmembrane transport / cellular response to amyloid-beta / calcium ion transport / chemical synaptic transmission / neuronal cell body / synapse / calcium ion binding / extracellular exosome / metal ion binding / plasma membrane 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: 3.1 Å | |||||||||
![]() | Gao Y / Qiu Y / Wei Y / Dong Y / Zhang XC / Zhao Y | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Molecular insights into the gating mechanisms of voltage-gated calcium channel Ca2.3. 著者: Yiwei Gao / Shuai Xu / Xiaoli Cui / Hao Xu / Yunlong Qiu / Yiqing Wei / Yanli Dong / Boling Zhu / Chao Peng / Shiqi Liu / Xuejun Cai Zhang / Jianyuan Sun / Zhuo Huang / Yan Zhao / ![]() 要旨: High-voltage-activated R-type Ca2.3 channel plays pivotal roles in many physiological activities and is implicated in epilepsy, convulsions, and other neurodevelopmental impairments. Here, we ...High-voltage-activated R-type Ca2.3 channel plays pivotal roles in many physiological activities and is implicated in epilepsy, convulsions, and other neurodevelopmental impairments. Here, we determine the high-resolution cryo-electron microscopy (cryo-EM) structure of human Ca2.3 in complex with the α2δ1 and β1 subunits. The VSD is stabilized in the resting state. Electrophysiological experiments elucidate that the VSD is not required for channel activation, whereas the other VSDs are essential for channel opening. The intracellular gate is blocked by the W-helix. A pre-W-helix adjacent to the W-helix can significantly regulate closed-state inactivation (CSI) by modulating the association and dissociation of the W-helix with the gate. Electrostatic interactions formed between the negatively charged domain on S6, which is exclusively conserved in the Ca2 family, and nearby regions at the alpha-interacting domain (AID) and S4-S5 helix are identified. Further functional analyses indicate that these interactions are critical for the open-state inactivation (OSI) of Ca2 channels. | |||||||||
履歴 |
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構造の表示
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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 | ![]() | 118.1 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 25 KB 25 KB | 表示 表示 | ![]() |
画像 | ![]() | 122.7 KB | ||
その他 | ![]() ![]() | 115.9 MB 115.9 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 | ![]() 7xlqMC 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: 1.04 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_33285_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_33285_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 R-type voltage-gated calcium channel CaV2.3-alpha2/delta1-b...
全体 | 名称: Human R-type voltage-gated calcium channel CaV2.3-alpha2/delta1-beta1 complex |
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要素 |
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-超分子 #1: Human R-type voltage-gated calcium channel CaV2.3-alpha2/delta1-b...
超分子 | 名称: Human R-type voltage-gated calcium channel CaV2.3-alpha2/delta1-beta1 complex タイプ: complex / ID: 1 / キメラ: Yes / 親要素: 0 / 含まれる分子: #1, #3, #2 |
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由来(天然) | 生物種: ![]() |
-分子 #1: Voltage-dependent R-type calcium channel subunit alpha-1E
分子 | 名称: Voltage-dependent R-type calcium channel subunit alpha-1E 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: 262.055984 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MARFGEAVVA RPGSGDGDSD QSRNRQGTPV PASGQAAAYK QTKAQRARTM ALYNPIPVRQ NCFTVNRSLF IFGEDNIVRK YAKKLIDWP PFEYMILATI IANCIVLALE QHLPEDDKTP MSRRLEKTEP YFIGIFCFEA GIKIVALGFI FHKGSYLRNG W NVMDFIVV ...文字列: MARFGEAVVA RPGSGDGDSD QSRNRQGTPV PASGQAAAYK QTKAQRARTM ALYNPIPVRQ NCFTVNRSLF IFGEDNIVRK YAKKLIDWP PFEYMILATI IANCIVLALE QHLPEDDKTP MSRRLEKTEP YFIGIFCFEA GIKIVALGFI FHKGSYLRNG W NVMDFIVV LSGILATAGT HFNTHVDLRT LRAVRVLRPL KLVSGIPSLQ IVLKSIMKAM VPLLQIGLLL FFAILMFAII GL EFYSGKL HRACFMNNSG ILEGFDPPHP CGVQGCPAGY ECKDWIGPND GITQFDNILF AVLTVFQCIT MEGWTTVLYN TND ALGATW NWLYFIPLII IGSFFVLNLV LGVLSGEFAK ERERVENRRA FMKLRRQQQI ERELNGYRAW IDKAEEVMLA EENK NAGTS ALEVLRRATI KRSRTEAMTR DSSDEHCVDI SSVGTPLARA SIKSAKVDGV SYFRHKERLL RISIRHMVKS QVFYW IVLS LVALNTACVA IVHHNQPQWL THLLYYAEFL FLGLFLLEMS LKMYGMGPRL YFHSSFNCFD FGVTVGSIFE VVWAIF RPG TSFGISVLRA LRLLRIFKIT KYWASLRNLV VSLMSSMKSI ISLLFLLFLF IVVFALLGMQ LFGGRFNFND GTPSANF DT FPAAIMTVFQ ILTGEDWNEV MYNGIRSQGG VSSGMWSAIY FIVLTLFGNY TLLNVFLAIA VDNLANAQEL TKDEQEEE E AFNQKHALQK AKEVSPMSAP NMPSIERDRR RRHHMSMWEP RSSHLRERRR RHHMSVWEQR TSQLRKHMQM SSQEALNRE EAPTMNPLNP LNPLSSLNPL NAHPSLYRRP RAIEGLALGL ALEKFEEERI SRGGSLKGDG GDRSSALDNQ RTPLSLGQRE PPWLARPCH GNCDPTQQEA GGGEAVVTFE DRARHRQSQR RSRHRRVRTE GKESSSASRS RSASQERSLD EAMPTEGEKD H ELRGNHGA KEPTIQEERA QDLRRTNSLM VSRGSGLAGG LDEADTPLVL PHPELEVGKH VVLTEQEPEG SSEQALLGNV QL DMGRVIS QSEPDLSCIT ANTDKATTES TSVTVAIPDV DPLVDSTVVH ISNKTDGEAS PLKEAEIRED EEEVEKKKQK KEK RETGKA MVPHSSMFIF STTNPIRRAC HYIVNLRYFE MCILLVIAAS SIALAAEDPV LTNSERNKVL RYFDYVFTGV FTFE MVIKM IDQGLILQDG SYFRDLWNIL DFVVVVGALV AFALANALGT NKGRDIKTIK SLRVLRVLRP LKTIKRLPKL KAVFD CVVT SLKNVFNILI VYKLFMFIFA VIAVQLFKGK FFYCTDSSKD TEKECIGNYV DHEKNKMEVK GREWKRHEFH YDNIIW ALL TLFTVSTGEG WPQVLQHSVD VTEEDRGPSR SNRMEMSIFY VVYFVVFPFF FVNIFVALII ITFQEQGDKM MEECSLE KN ERACIDFAIS AKPLTRYMPQ NRHTFQYRVW HFVVSPSFEY TIMAMIALNT VVLMMKYYSA PCTYELALKY LNIAFTMV F SLECVLKVIA FGFLNYFRDT WNIFDFITVI GSITEIILTD SKLVNTSGFN MSFLKLFRAA RLIKLLRQGY TIRILLWTF VQSFKALPYV CLLIAMLFFI YAIIGMQVFG NIKLDEESHI NRHNNFRSFF GSLMLLFRSA TGEAWQEIML SCLGEKGCEP DTTAPSGQN ENERCGTDLA YVYFVSFIFF CSFLMLNLFV AVIMDNFEYL TRDSSILGPH HLDEFVRVWA EYDRAACGRI H YTEMYEML TLMSPPLGLG KRCPSKVAYK RLVLMNMPVA EDMTVHFTST LMALIRTALD IKIAKGGADR QQLDSELQKE TL AIWPHLS QKMLDLLVPM PKASDLTVGK IYAAMMIMDY YKQSKVKKQR QQLEEQKNAP MFQRMEPSSL PQEIIANAKA LPY LQQDPV SGLSGRSGYP SMSPLSPQDI FQLACMDPAD DGQFQERQSL EPEVSELKSV QPSNHGIYLP SDTQEHAGSG RASS MPRLT VDPQVVTDPS SMRRSFSTIR DKRSNSSWLE EFSMERSSEN TYKSRRRSYH SSLRLSAHRL NSDSGHKSDT HRSGG RERG RSKERKHLLS PDVSRCNSEE RGTQADWESP ERRQSRSPSE GRSQTPNRQG TGSLSESSIP SVSDTSTPRR SRRQLP PVP PKPRPLLSYS SLIRHAGSIS PPADGSEEGS PLTSQALESN NACLTESSNS PHPQQSQHAS PQRYISEPYL ALHEDSH AS DCGEEETLTF EAAVATSLGR SNTIGSAPPL RHSWQMPNGH YRRRRRGGPG PGMMCGAVNN LLSDTEEDDK C |
-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: 122.034352 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: FPSAVTIKSW VDKMQEDLVT LAKTASGVNQ LVDIYEKYQD LYTVEPNNAR QLVEIAARDI EKLLSNRSKA LVRLALEAEK VQAAHQWRE DFASNEVVYY NAKDDLDPEK NDSEPGSQRI KPVFIEDANF GRQISYQHAA VHIPTDIYEG STIVLNELNW T SALDEVFK ...文字列: FPSAVTIKSW VDKMQEDLVT LAKTASGVNQ LVDIYEKYQD LYTVEPNNAR QLVEIAARDI EKLLSNRSKA LVRLALEAEK VQAAHQWRE DFASNEVVYY NAKDDLDPEK NDSEPGSQRI KPVFIEDANF GRQISYQHAA VHIPTDIYEG STIVLNELNW T SALDEVFK KNREEDPSLL WQVFGSATGL ARYYPASPWV DNSRTPNKID LYDVRRRPWY IQGAASPKDM LILVDVSGSV SG LTLKLIR TSVSEMLETL SDDDFVNVAS FNSNAQDVSC FQHLVQANVR NKKVLKDAVN NITAKGITDY KKGFSFAFEQ LLN YNVSRA NCNKIIMLFT DGGEERAQEI FNKYNKDKKV RVFTFSVGQH NYDRGPIQWM ACENKGYYYE IPSIGAIRIN TQEY LDVLG RPMVLAGDKA KQVQWTNVYL DALELGLVIT GTLPVFNITG QFENKTNLKN QLILGVMGVD VSLEDIKRLT PRFTL CPNG YYFAIDPNGY VLLHPNLQPK PIGVGIPTIN LRKRRPNIQN PKSQEPVTLD FLDAELENDI KVEIRNKMID GESGEK TFR TLVKSQDERY IDKGNRTYTW TPVNGTDYSL ALVLPTYSFY YIKAKLEETI TQARYSETLK PDNFEESGYT FIAPRDY CN DLKISDNNTE FLLNFNEFID RKTPNNPSCN ADLINRVLLD AGFTNELVQN YWSKQKNIKG VKARFVVTDG GITRVYPK E AGENWQENPE TYEDSFYKRS LDNDNYVFTA PYFNKSGPGA YESGIMVSKA VEIYIQGKLL KPAVVGIKID VNSWIENFT KTSIRDPCAG PVCDCKRNSD VMDCVILDDG GFLLMANHDD YTNQIGRFFG EIDPSLMRHL VNISVYAFNK SYDYQSVCEP GAAPKQGAG HRSAYVPSVA DILQIGWWAT AAAWSILQQF LLSLTFPRLL EAVEMEDDDF TASLSKQSCI TEQTQYFFDN D SKSFSGVL DCGNCSRIFH GEKLMNTNLI FIMVESKGTC PCDTRLLIQA EQTSDGPNPC DMVKQPRYRK GPDVCFDNNV LE DYTDCGG VSGLNPSLWY IIGIQFLLLW LVSGSTHRLL |
-分子 #3: Voltage-dependent L-type calcium channel subunit beta-1
分子 | 名称: Voltage-dependent L-type calcium channel subunit beta-1 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: 65.799594 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MVQKTSMSRG PYPPSQEIPM EVFDPSPQGK YSKRKGRFKR SDGSTSSDTT SNSFVRQGSA ESYTSRPSDS DVSLEEDREA LRKEAERQA LAQLEKAKTK PVAFAVRTNV GYNPSPGDEV PVQGVAITFE PKDFLHIKEK YNNDWWIGRL VKEGCEVGFI P SPVKLDSL ...文字列: MVQKTSMSRG PYPPSQEIPM EVFDPSPQGK YSKRKGRFKR SDGSTSSDTT SNSFVRQGSA ESYTSRPSDS DVSLEEDREA LRKEAERQA LAQLEKAKTK PVAFAVRTNV GYNPSPGDEV PVQGVAITFE PKDFLHIKEK YNNDWWIGRL VKEGCEVGFI P SPVKLDSL RLLQEQKLRQ NRLGSSKSGD NSSSSLGDVV TGTRRPTPPA SAKQKQKSTE HVPPYDVVPS MRPIILVGPS LK GYEVTDM MQKALFDFLK HRFDGRISIT RVTADISLAK RSVLNNPSKH IIIERSNTRS SLAEVQSEIE RIFELARTLQ LVA LDADTI NHPAQLSKTS LAPIIVYIKI TSPKVLQRLI KSRGKSQSKH LNVQIAASEK LAQCPPEMFD IILDENQLED ACEH LAEYL EAYWKATHPP SSTPPNPLLN RTMATAALAA SPAPVSNLQG PYLASGDQPL ERATGEHASM HEYPGELGQP PGLYP SSHP PGRAGTLRAL SRQDTFDADT PGSRNSAYTE LGDSCVDMET DPSEGPGLGD PAGGGTPPAR QGSWEDEEED YEEELT DNR NRGRNKARYC AEGGGPVLGR NKNELEGWGR GVYIR |
-分子 #6: CHOLESTEROL HEMISUCCINATE
分子 | 名称: CHOLESTEROL HEMISUCCINATE / タイプ: ligand / ID: 6 / コピー数: 6 / 式: Y01 |
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分子量 | 理論値: 486.726 Da |
Chemical component information | ![]() ChemComp-Y01: |
-分子 #7: HEXADECANE
分子 | 名称: HEXADECANE / タイプ: ligand / ID: 7 / コピー数: 7 / 式: R16 |
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分子量 | 理論値: 226.441 Da |
Chemical component information | ![]() ChemComp-R16: |
-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: CALCIUM ION
分子 | 名称: CALCIUM ION / タイプ: ligand / ID: 9 / コピー数: 2 / 式: CA |
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分子量 | 理論値: 40.078 Da |
-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: 8 / 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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![]() | 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 | 5 mg/mL |
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緩衝液 | pH: 7.5 |
グリッド | モデル: Quantifoil R1.2/1.3 / 材質: COPPER / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 60 sec. |
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 |
詳細 | This sample was obtained from the monodispersed peak fractions of the size-exclusion chromatography. |
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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) 検出モード: SUPER-RESOLUTION / デジタル化 - サイズ - 横: 7676 pixel / デジタル化 - サイズ - 縦: 7420 pixel / デジタル化 - 画像ごとのフレーム数: 1-32 / 撮影したグリッド数: 1 / 実像数: 2097 / 平均露光時間: 6.7 sec. / 平均電子線量: 60.0 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 / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.2 µm / 最小 デフォーカス(公称値): 1.2 µm / 倍率(公称値): 130000 |
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 |