+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-32370 | |||||||||
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タイトル | Cryo-EM structure of human Nav1.7(E406K) in complex with auxiliary beta subunits, ProTx-II and tetrodotoxin (S6IV pi helix conformer) | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / detection of mechanical stimulus involved in sensory perception / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / membrane depolarization during Purkinje myocyte cell action potential / regulation of atrial cardiac muscle cell membrane depolarization ...corticospinal neuron axon guidance / positive regulation of voltage-gated sodium channel activity / response to pyrethroid / detection of mechanical stimulus involved in sensory perception / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transporter activity / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / membrane depolarization during Purkinje myocyte cell action potential / regulation of atrial cardiac muscle cell membrane depolarization / cardiac conduction / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / node of Ranvier / cardiac muscle cell action potential involved in contraction / regulation of ventricular cardiac muscle cell membrane repolarization / voltage-gated sodium channel complex / sodium channel inhibitor activity / locomotion / neuronal action potential propagation / Interaction between L1 and Ankyrins / voltage-gated sodium channel activity / sodium ion transport / behavioral response to pain / Phase 0 - rapid depolarisation / regulation of heart rate by cardiac conduction / detection of temperature stimulus involved in sensory perception of pain / membrane depolarization / intercalated disc / sodium ion transmembrane transport / sodium channel regulator activity / cardiac muscle contraction / sensory perception of pain / T-tubule / post-embryonic development / axon guidance / response to toxic substance / Sensory perception of sweet, bitter, and umami (glutamate) taste / positive regulation of neuron projection development / circadian rhythm / nervous system development / gene expression / response to heat / chemical synaptic transmission / perikaryon / transmembrane transporter binding / cell adhesion / inflammatory response / axon / synapse / extracellular region / plasma membrane 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: 3.0 Å | |||||||||
データ登録者 | Yan N / Huang G / Liu D / Wei P / Shen H | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Cell Rep / 年: 2022 タイトル: High-resolution structures of human Na1.7 reveal gating modulation through α-π helical transition of S6. 著者: Gaoxingyu Huang / Dongliang Liu / Weipeng Wang / Qiurong Wu / Jiaofeng Chen / Xiaojing Pan / Huaizong Shen / Nieng Yan / 要旨: Na1.7 represents a preeminent target for next-generation analgesics for its critical role in pain sensation. Here we report a 2.2-Å resolution cryo-EM structure of wild-type (WT) Na1.7 complexed ...Na1.7 represents a preeminent target for next-generation analgesics for its critical role in pain sensation. Here we report a 2.2-Å resolution cryo-EM structure of wild-type (WT) Na1.7 complexed with the β1 and β2 subunits that reveals several previously indiscernible cytosolic segments. Reprocessing of the cryo-EM data for our reported structures of Na1.7(E406K) bound to various toxins identifies two distinct conformations of S6, one composed of α helical turns only and the other containing a π helical turn in the middle. The structure of ligand-free Na1.7(E406K), determined at 3.5-Å resolution, is identical to the WT channel, confirming that binding of Huwentoxin IV or Protoxin II to VSD allosterically induces the α → π transition of S6. The local secondary structural shift leads to contraction of the intracellular gate, closure of the fenestration on the interface of repeats I and IV, and rearrangement of the binding site for the fast inactivation motif. | |||||||||
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_32370.map.gz | 48.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-32370-v30.xml emd-32370.xml | 15.9 KB 15.9 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_32370.png | 64.7 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-32370 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32370 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_32370_validation.pdf.gz | 523.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_32370_full_validation.pdf.gz | 523.5 KB | 表示 | |
XML形式データ | emd_32370_validation.xml.gz | 6.2 KB | 表示 | |
CIF形式データ | emd_32370_validation.cif.gz | 7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32370 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32370 | 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_32370.map.gz / 形式: CCP4 / 大きさ: 52.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.091 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
-試料の構成要素
-全体 : Human voltage-gated sodium channel Nav1.7 in complex with auxilia...
全体 | 名称: Human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunits |
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要素 |
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-超分子 #1: Human voltage-gated sodium channel Nav1.7 in complex with auxilia...
超分子 | 名称: Human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunits タイプ: complex / キメラ: Yes / 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) |
組換発現 | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 279.99 kDa/nm |
-分子 #1: Sodium channel protein type 9 subunit alpha
分子 | 名称: Sodium channel protein type 9 subunit alpha / 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: 231.211922 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MASWSHPQFE KGGGARGGSG GGSWSHPQFE KGFDYKDDDD KGTMAMLPPP GPQSFVHFTK QSLALIEQRI AERKSKEPKE EKKDDDEEA PKPSSDLEAG KQLPFIYGDI PPGMVSEPLE DLDPYYADKK TFIVLNKGKT IFRFNATPAL YMLSPFSPLR R ISIKILVH ...文字列: MASWSHPQFE KGGGARGGSG GGSWSHPQFE KGFDYKDDDD KGTMAMLPPP GPQSFVHFTK QSLALIEQRI AERKSKEPKE EKKDDDEEA PKPSSDLEAG KQLPFIYGDI PPGMVSEPLE DLDPYYADKK TFIVLNKGKT IFRFNATPAL YMLSPFSPLR R ISIKILVH SLFSMLIMCT ILTNCIFMTM NNPPDWTKNV EYTFTGIYTF ESLVKILARG FCVGEFTFLR DPWNWLDFVV IV FAYLTEF VNLGNVSALR TFRVLRALKT ISVIPGLKTI VGALIQSVKK LSDVMILTVF CLSVFALIGL QLFMGNLKHK CFR NSLENN ETLESIMNTL ESEEDFRKYF YYLEGSKDAL LCGFSTDSGQ CPEGYTCVKI GRNPDYGYTS FDTFSWAFLA LFRL MTQDY WENLYQQTLR AAGKTYMIFF VVVIFLGSFY LINLILAVVA MAYKEQNQAN IEEAKQKELE FQQMLDRLKK EQEEA EAIA AAAAEYTSIR RSRIMGLSES SSETSKLSSK SAKERRNRRK KKNQKKLSSG EEKGDAEKLS KSESEDSIRR KSFHLG VEG HRRAHEKRLS TPNQSPLSIR GSLFSARRSS RTSLFSFKGR GRDIGSETEF ADDEHSIFGD NESRRGSLFV PHRPQER RS SNISQASRSP PMLPVNGKMH SAVDCNGVVS LVDGRSALML PNGQLLPEVI IDKATSDDSG TTNQIHKKRR CSSYLLSE D MLNDPNLRQR AMSRASILTN TVEELEESRQ KCPPWWYRFA HKFLIWNCSP YWIKFKKCIY FIVMDPFVDL AITICIVLN TLFMAMEHHP MTEEFKNVLA IGNLVFTGIF AAEMVLKLIA MDPYEYFQVG WNIFDSLIVT LSLVELFLAD VEGLSVLRSF RLLRVFKLA KSWPTLNMLI KIIGNSVGAL GNLTLVLAII VFIFAVVGMQ LFGKSYKECV CKINDDCTLP RWHMNDFFHS F LIVFRVLC GEWIETMWDC MEVAGQAMCL IVYMMVMVIG NLVVLNLFLA LLLSSFSSDN LTAIEEDPDA NNLQIAVTRI KK GINYVKQ TLREFILKAF SKKPKISREI RQAEDLNTKK ENYISNHTLA EMSKGHNFLK EKDKISGFGS SVDKHLMEDS DGQ SFIHNP SLTVTVPIAP GESDLENMNA EELSSDSDSE YSKVRLNRSS SSECSTVDNP LPGEGEEAEA EPMNSDEPEA CFTD GCVWR FSCCQVNIES GKGKIWWNIR KTCYKIVEHS WFESFIVLMI LLSSGALAFE DIYIERKKTI KIILEYADKI FTYIF ILEM LLKWIAYGYK TYFTNAWCWL DFLIVDVSLV TLVANTLGYS DLGPIKSLRT LRALRPLRAL SRFEGMRVVV NALIGA IPS IMNVLLVCLI FWLIFSIMGV NLFAGKFYEC INTTDGSRFP ASQVPNRSEC FALMNVSQNV RWKNLKVNFD NVGLGYL SL LQVATFKGWT IIMYAAVDSV NVDKQPKYEY SLYMYIYFVV FIIFGSFFTL NLFIGVIIDN FNQQKKKLGG QDIFMTEE Q KKYYNAMKKL GSKKPQKPIP RPGNKIQGCI FDLVTNQAFD ISIMVLICLN MVTMMVEKEG QSQHMTEVLY WINVVFIIL FTGECVLKLI SLRHYYFTVG WNIFDFVVVI ISIVGMFLAD LIETYFVSPT LFRVIRLARI GRILRLVKGA KGIRTLLFAL MMSLPALFN IGLLLFLVMF IYAIFGMSNF AYVKKEDGIN DMFNFETFGN SMICLFQITT SAGWDGLLAP ILNSKPPDCD P KKVHPGSS VEGDCGNPSV GIFYFVSYII ISFLVVVNMY IAVILENFSV ATEESTEPLS EDDFEMFYEV WEKFDPDATQ FI EFSKLSD FAAALDPPLL IAKPNKVQLI AMDLPMVSGD RIHCLDILFA FTKRVLGESG EMDSLRSQME ERFMSANPSK VSY EPITTT LKRKQEDVSA TVIQRAYRRY RLRQNVKNIS SIYIKDGDRD DDLLNKKDMA FDNVNENSSP EKTDATSSTT SPPS YDSVT KPDKEKYEQD RTEKEDKGKD SKESKK |
-分子 #2: Sodium channel subunit beta-1
分子 | 名称: Sodium channel 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: Homo sapiens (ヒト) |
分子量 | 理論値: 24.732115 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MGRLLALVVG AALVSSACGG CVEVDSETEA VYGMTFKILC ISCKRRSETN AETFTEWTFR QKGTEEFVKI LRYENEVLQL EEDERFEGR VVWNGSRGTK DLQDLSIFIT NVTYNHSGDY ECHVYRLLFF ENYEHNTSVV KKIHIEVVDK ANRDMASIVS E IMMYVLIV ...文字列: MGRLLALVVG AALVSSACGG CVEVDSETEA VYGMTFKILC ISCKRRSETN AETFTEWTFR QKGTEEFVKI LRYENEVLQL EEDERFEGR VVWNGSRGTK DLQDLSIFIT NVTYNHSGDY ECHVYRLLFF ENYEHNTSVV KKIHIEVVDK ANRDMASIVS E IMMYVLIV VLTIWLVAEM IYCYKKIAAA TETAAQENAS EYLAITSESK ENCTGVQVAE |
-分子 #3: Sodium channel subunit beta-2
分子 | 名称: Sodium channel subunit beta-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: Homo sapiens (ヒト) |
分子量 | 理論値: 24.355859 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MHRDAWLPRP AFSLTGLSLF FSLVPPGRSM EVTVPATLNV LNGSDARLPC TFNSCYTVNH KQFSLNWTYQ ECNNCSEEMF LQFRMKIIN LKLERFQDRV EFSGNPSKYD VSVMLRNVQP EDEGIYNCYI MNPPDRHRGH GKIHLQVLME EPPERDSTVA V IVGASVGG ...文字列: MHRDAWLPRP AFSLTGLSLF FSLVPPGRSM EVTVPATLNV LNGSDARLPC TFNSCYTVNH KQFSLNWTYQ ECNNCSEEMF LQFRMKIIN LKLERFQDRV EFSGNPSKYD VSVMLRNVQP EDEGIYNCYI MNPPDRHRGH GKIHLQVLME EPPERDSTVA V IVGASVGG FLAVVILVLM VVKCVRRKKE QKLSTDDLKT EEEGKTDGEG NPDDGAK |
-分子 #5: (1R,5R,6R,7R,9S,11S,12S,13S,14S)-3-amino-14-(hydroxymethyl)-8,10-...
分子 | 名称: (1R,5R,6R,7R,9S,11S,12S,13S,14S)-3-amino-14-(hydroxymethyl)-8,10-dioxa-2,4-diazatetracyclo[7.3.1.1~7,11~.0~1,6~]tetradec-3-ene-5,9,12,13,14-pentol (non-preferred name) タイプ: ligand / ID: 5 / コピー数: 1 / 式: 9SR |
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分子量 | 理論値: 319.268 Da |
Chemical component information | ChemComp-9SR: |
-分子 #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 6 / コピー数: 6 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-分子 #7: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phospho...
分子 | 名称: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine タイプ: ligand / ID: 7 / コピー数: 1 / 式: P5S |
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分子量 | 理論値: 792.075 Da |
Chemical component information | ChemComp-P5S: |
-分子 #8: CHOLESTEROL HEMISUCCINATE
分子 | 名称: CHOLESTEROL HEMISUCCINATE / タイプ: ligand / ID: 8 / コピー数: 5 / 式: Y01 |
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分子量 | 理論値: 486.726 Da |
Chemical component information | ChemComp-Y01: |
-分子 #9: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE
分子 | 名称: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE / タイプ: ligand / ID: 9 / コピー数: 1 / 式: LPE |
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分子量 | 理論値: 510.708 Da |
Chemical component information | ChemComp-LPE: |
-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 |
-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: 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): 1.8 µm / 最小 デフォーカス(公称値): 1.5 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: EMDB MAP EMDB ID: |
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最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.0 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 188952 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |