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データを開く
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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Structure of mouse RyR1 in complex with S100A1 (EGTA-only dataset) | |||||||||
![]() | RyR1 with S100A1, EGTA | |||||||||
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![]() | Calcium / Ion Channel / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() junctional membrane complex / TGF-beta receptor signaling activates SMADs / Calcineurin activates NFAT / mTORC1-mediated signalling / regulation of response to osmotic stress / cytoplasmic side of membrane / regulation of muscle contraction / sarcoplasmic reticulum calcium ion transport / transforming growth factor beta receptor binding / Stimuli-sensing channels ...junctional membrane complex / TGF-beta receptor signaling activates SMADs / Calcineurin activates NFAT / mTORC1-mediated signalling / regulation of response to osmotic stress / cytoplasmic side of membrane / regulation of muscle contraction / sarcoplasmic reticulum calcium ion transport / transforming growth factor beta receptor binding / Stimuli-sensing channels / type I transforming growth factor beta receptor binding / Ion homeostasis / heart trabecula formation / terminal cisterna / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / S100 protein binding / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / response to caffeine / ossification involved in bone maturation / ventricular cardiac muscle tissue morphogenesis / skin development / cellular response to ATP / regulation of heart contraction / organelle membrane / FK506 binding / cellular response to caffeine / positive regulation of sprouting angiogenesis / outflow tract morphogenesis / extrinsic component of cytoplasmic side of plasma membrane / regulation of ryanodine-sensitive calcium-release channel activity / smooth endoplasmic reticulum / voltage-gated calcium channel activity / skeletal muscle fiber development / striated muscle contraction / heart morphogenesis / muscle contraction / T cell proliferation / axon terminus / release of sequestered calcium ion into cytosol / regulation of cytosolic calcium ion concentration / sarcoplasmic reticulum membrane / calcium channel complex / T-tubule / Hsp70 protein binding / cellular response to calcium ion / sarcomere / negative regulation of transforming growth factor beta receptor signaling pathway / sarcoplasmic reticulum / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / calcium channel activity / cytoplasmic side of plasma membrane / sarcolemma / Z disc / cytokine-mediated signaling pathway / calcium ion transport / ATPase binding / protease binding / protein homotetramerization / vesicle / transmembrane transporter binding / calmodulin binding / synapse / calcium ion binding / perinuclear region of cytoplasm / enzyme binding / Golgi apparatus / protein homodimerization activity / protein-containing complex / mitochondrion / nucleoplasm / ATP binding / identical protein binding / membrane / cytoplasm / cytosol 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: 3.21 Å | |||||||||
![]() | Weninger G / Marks AR | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into the regulation of RyR1 by S100A1. 著者: Gunnar Weninger / Marco C Miotto / Carl Tchagou / Steven Reiken / Haikel Dridi / Sören Brandenburg / Gabriel C Riedemann / Qi Yuan / Yang Liu / Alexander Chang / Anetta Wronska / Stephan E ...著者: Gunnar Weninger / Marco C Miotto / Carl Tchagou / Steven Reiken / Haikel Dridi / Sören Brandenburg / Gabriel C Riedemann / Qi Yuan / Yang Liu / Alexander Chang / Anetta Wronska / Stephan E Lehnart / Andrew R Marks / ![]() ![]() 要旨: S100A1, a small homodimeric EF-hand Ca-binding protein (~21 kDa), plays an important regulatory role in Ca signaling pathways involved in various biological functions including Ca cycling and ...S100A1, a small homodimeric EF-hand Ca-binding protein (~21 kDa), plays an important regulatory role in Ca signaling pathways involved in various biological functions including Ca cycling and contractile performance in skeletal and cardiac myocytes. One key target of the S100A1 interactome is the ryanodine receptor (RyR), a huge homotetrameric Ca release channel (~2.3 MDa) of the sarcoplasmic reticulum. Here, we report cryoelectron microscopy structures of S100A1 bound to RyR1, the skeletal muscle isoform, in absence and presence of Ca. Ca-free apo-S100A1 binds beneath the bridging solenoid (BSol) and forms contacts with the junctional solenoid and the shell-core linker of RyR1. Upon Ca-binding, S100A1 undergoes a conformational change resulting in the exposure of the hydrophobic pocket known to serve as a major interaction site of S100A1. Through interactions of the hydrophobic pocket with RyR1, Ca-bound S100A1 intrudes deeper into the RyR1 structure beneath BSol than the apo-form and induces sideways motions of the C-terminal BSol region toward the adjacent RyR1 protomer resulting in tighter interprotomer contacts. Interestingly, the second hydrophobic pocket of the S100A1-dimer is largely exposed at the hydrophilic surface making it prone to interactions with the local environment, suggesting that S100A1 could be involved in forming larger heterocomplexes of RyRs with other protein partners. Since S100A1 interactions stabilizing BSol are implicated in the regulation of RyR-mediated Ca release, the characterization of the S100A1 binding site conserved between RyR isoforms may provide the structural basis for the development of therapeutic strategies regarding treatments of RyR-related disorders. | |||||||||
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マップデータ | ![]() | 35.6 MB | ![]() | |
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-関連構造データ
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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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ファイル | ![]() | ||||||||||||||||||||
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注釈 | RyR1 with S100A1, EGTA | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.837 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 : Complex of RyR1 with Calstabin-1 and S100A1 (EGTA condition)
全体 | 名称: Complex of RyR1 with Calstabin-1 and S100A1 (EGTA condition) |
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要素 |
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-超分子 #1: Complex of RyR1 with Calstabin-1 and S100A1 (EGTA condition)
超分子 | 名称: Complex of RyR1 with Calstabin-1 and S100A1 (EGTA condition) 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: Ryanodine receptor 1
分子 | 名称: Ryanodine receptor 1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 565.692562 KDa |
配列 | 文字列: MGDGGGEGED EVQFLRTDDE VVLQCSATVL KEQLKLCLAA EGFGNRLCFL EPTSNAQNVP PDLAICCFIL EQSLSVRALQ EMLANTVEA GVESSQGGGH RTLLYGHAIL LRHAHSRMYL SCLTTSRSMT DKLAFDVGLQ EDATGEACWW TMHPASKQRS E GEKVRVGD ...文字列: MGDGGGEGED EVQFLRTDDE VVLQCSATVL KEQLKLCLAA EGFGNRLCFL EPTSNAQNVP PDLAICCFIL EQSLSVRALQ EMLANTVEA GVESSQGGGH RTLLYGHAIL LRHAHSRMYL SCLTTSRSMT DKLAFDVGLQ EDATGEACWW TMHPASKQRS E GEKVRVGD DLILVSVSSE RYLHLSTASG ELQVDASFMQ TLWNMNPICS GCEEGFVTGG HVLRLFHGHM DECLTISPSD SD DQRRLVY YEGGPVCTHA RSLWRLEPLR ISWSGSHLRW GQPLRIRHVT TGRYLGLTED QGLVVVDASK AHTKATSFCF RIS KEKLDV APKRDVEGMG PPEIKYGESL CFVQHVASGL WLTYAAPDPK ALRLGVLKKK AMLHQEGHMD DALSLTRCQQ EESQ AARMI YSTAGLYNQF IKGLDSFSGK PRGSGPPAGS ALPIEGVILS LQDLIGYFEP PSEELQHEEK QTKLRSLRNR QSLFQ EEGM LSLVLNCIDR LNVYTTAAHF AEFAGEEAAE SWKEIVNLLY ELLASLIRGN RTNCALFSTN LDWLVSKLDR LEASSG ILE VLYCVLIESP EVLNIIQENH IKSIISLLDK HGRNHKVLDV LCSLCVCNGV AVRSNQDLIT ENLLPGRELL LQTNLIN YV TSIRPNIFVG RAEGSTQYGK WYFEVMVDEV APFLTAQATH LRVGWALSEG YSPYPGGGEG WGGNGVGDDL YSYGFDGL H LWTGHVARPV TSPGQHLLAP EDVVSCCLDL SVPSISFRIN GCPVQGVFES FNLDGLFFPV VSFSAGIKVR FLLGGRHGE FKFLPPPGYA PCHEAVLPRE RLHLQPIKEY RREGPRGPHL VGPSRCLSHL DFVPCPVDTI QIVLPPHLER IREKLAENIH ELWALTRIE QGWTYGPVRD DNKRLHPCLV NFHSLPEPER NYNLQMSGET LKTLLALGCH VGMADEKAED NLKKTKLPKT Y MMSNGYKP APLDLSHVRL TPAQTTLVDR LAENGHNVWA RDRVAQGWSY SAVQDIPARR NPRLVPYRLL DEATKRSNRD SL CQAVRTL LGYGYNIEPP DQEPSQVDSQ SRGDRARIFR AEKSYAVQSG RWYFEFEAVT TGEMRVGWAR PELRPDVELG ADD LAYVFN GHRGQRWHLG SEPFGRPWQS GDVVGCMIDL TENTIIFTLN GEVLMSDSGS ETAFRDIEIG DGFLPVCSLG PGQV GHLNL GQDVSSLRFF AICGLQEGFE PFAINMQRPV TTWFSKSLPQ FEPVPLEHPH YEVARMDGTV DTPPCLRLTH RTWGS QNSL VEMLFLRLSL PVQFHQHFRC TAGATPLASP GLQPPAEDEA RAAEPDTDYE NLRRSAGGWG EAEGGKDGTA KEGTPG GTA QAGVEAQPAR AENEKDATTE KNKKRGFLFK AKKVAMMTQP PSTPALPRLP RDVVPADNRD DPEIILNTTT YYYSVRV FA GQEPSCVWVG WVTPDYHQHD MSFDLSKVRA VTVTMGDEQG NVHSSLKCSN CYMVWGGDFV SPGQQGRISH TDLVIGCL V DLATGLMTFT ANGKESNTFF QVEPNTKLFP AVFVLPTHQN VVQFELGKQK NIMPLSAAMF LSERKNPAPQ CPPRLEVQM LMPVSWSRMP NHFLQVDTRR AGERLGWAVQ CQEPLMMMAL HIPEENRCMD ILELSERLDL QRFHSHTLSL YRSVCALGNN RVAHALCSH VDQAQLLHAL EDARLPGPLR AGYYDLLISI HLESACRSRR SMLSEYIVPL TPETRAITLF PPGRSAEDGP R RHGLPGVG VTTSLRPPHH FSPPCFVVAL PAAGATEAPA RLSPAIPLEA LRDKALRMLG EAVRDGGQHA RDPVGGSVEF QF VPVLKLV STLLVMGVFS DEDVKQILKM IEPEVFREEE EVEEEGEEEE EDEEEKEEDE EEEAHEKEDE EKEEAEDAAE EEK EELEEG LLQMKLPESV KLQMCHLLEY FCDQELQHRV ESLAAFAECY VDKMQGNQRG RYGLLMKAFT MSAAETARRT REFR SPPQE QINMLLHFKN GADEEECPLP EEIRQELVNF HQDLLAHCGI QLEGEEEEPE EESTLGSRLM SLLEKVKLVK KTEEK PEEE PAPEEHKPQS LQELVSHTVV RWAQEDFVQS PELVRAMFSL LHRQYDGLGE LLRALPRAYT ISVSSVEDTM SLLECL GQI RSLLIVQMGP QEENLMIQSI GNIMNNKVFY QHPNLMRALG MHETVMEVMV NVLGGGESKE IRFPKMVTSC CRFLCYF CR ISRQNQRSMF DHLSYLLENS GIGLGMQGST PLDVAAASVI DNNELALALQ EQDLEKVVSY LAGCGLQSCP MLLAKGYP D IGWNPCGGER YLDFLRFAVF VNGESVEENA NVVVRLLIRK PECFGPALRG EGGSGLLAAI EEAIRISEDP ARDGPGVRR DRRREHFGEE PPEENRVHLG HAIMSFYAAL IDLLGRCAPE THLIQAGKGE ALRIRAILRS LVPLDDLVGI ISLPLQIPTL GKDGALVQP KMSASFVPDH KASMVLFLDR VYGIENQDFL LHVLDVGFLP DMRAAASLDT ATFSTTEMAL ALNRYLCLAV L PLITKCAP LFAGTEHRAI MVDSMLHTVY RLSRGRSLTK AQRDVIEDCL MALCRYIRPS MLQHLLRRLV FDVPILNEFA KM PLKLLTN HYERCWKYYC LPTGWANFGV TSEEELHLTR KLFWGIFDSL AHKKYDQELY RIAMPCLCAI AGALPPDYVD ASY SSKTEK KATVDAEGNF DPRPVETLNV IIPEKLDSFI NKFAEYTHEK WAFDKIQNNW SYGENIDEEL KTHPMLRPYK TFSE KDKEI YRWPIKESLK AMIAWEWTVE KAREGEEEKT EKKKTRKISQ TAQTYDPREG YNPQPPDLSV VTLSRELQAM AEQLA ENYH NTWGRKKKQE LEAKGGGSHP LLVPYDTLTA KEKARDREKA QELLKFLQMN GYAVTRGLKD MELDTSSIEK RFAFGF LQQ LLRWMDISQE FIAHLEAVVS SGRVEKSPHE QEIKFFAKIL LPLINQYFTN HCLYFLSTPA KVLGSGGHAS NKEKEMI TS LFCKLAALVR HRVSLFGTDA PAVVNCLHIL ARSLDARTVM KSGPEIVKAG LRSFFESASE DIEKMVENLR LGKVSQAR T QVKGVGQNLT YTTVALLPVL TTLFQHIAQH QFGDDVILDD VQVSCYRTLC SIYSLGTTRN PYVEKLRPAL GECLARLAA AMPVAFLEPE LNEYNACSVY TTKSPRERAI LGLPNSVEEM CPDIPVLERL MAEIGGLAES GARYTEMPHV IEITLPMLCS YLPRWWERG PEAPPPALPA GAPPPCTAVT SDHLNSLLGN ILRIIVNNLG IDEASWMKRL AVFAQPIVSR ARPELLRSHF I PTIGRLRK RAGKVVAEEE QLRLEAKAEA EEGELLVRDE FSVLCRDLYA LYPLLIRYVD NNRAHWLTEP NPNAEELFRM VG EIFIYWS KSHNFKREEQ NFVVQNEINN MSFLTADNKS KMAKAGDVQS GGSDQERTKK KRRGDRYSVQ TSLIVATLKK MLP IGLNMC APTDQDLIVL AKARYALKDT DEEVREFLQN NLNLQGKVEG SPSLRWQMAL YRGVPGREED ADDPEKIVRR VQEV SAVLY HLDQTEHPYK SKKAVWHKLL SKQRRRAVVA CFRMTPLYNL PTHRACNMFL ESYKASWILT EDHSFEDRMI DDLSK AGEQ EEEEEEVEEK KPDPLHQLVL HFSRTALTEK SKLDEDYLYM AYADIMAKSC HLEEGGENGE EGGEEEEVEV SFEEKE MEK QRLLYQQSRL HNRGAAEMVL QMISACKGET GAMVSSTLKL GISILNGGNA EVQQKMLDYL KDKKEVGFFQ SIQALMQ TC SVLDLNAFER QNKAEGLGMV NEDGTVINRQ NGEKVMADDE FTQDLFRFLQ LLCEGHNNDF QNYLRTQTGN TTTINIII C TVDYLLRLQE SISDFYWYYS GKDVIEEQGK RNFSKAMSVA KQVFNSLTEY IQGPCTGNQQ SLAHSRLWDA VVGFLHVFA HMMMKLAQDS SQIELLKELL DLQKDMVVML LSLLEGNVVN GMIARQMVDM LVESSSNVEM ILKFFDMFLK LKDIVGSEAF QDYVTDPRG LISKKDFQKA MDSQKQFTGP EIQFLLSCSE ADENEMINCE EFANRFQEPA RDIGFNVAVL LTNLSEHVPH D PRLRNFLE LAESILEYFR PYLGRIEIMG ASRRIERIYF EISETNRAQW EMPQVKESKR QFIFDVVNEG GESEKMEMFV SF CEDTIFE MQIAAQISEP EGEPEEDEDE GAEEAEEGAA GSDGSGSAAA AGVWVWLAAT AGRTLRGLSY RSLRRRVRRL RRL TAREAA TAVAALLWAL VTRAGGAGAG AAAGALRLLW GSLFGGGLVD SAKKVTVTEL LAGMPDPTGD EVHGQQPSGA GSDA EGEGE GEGEGDAADG AGDEEAAADQ AGTGGADGAV AVADGSPFRP EGAGGLGDMG DTTPVEPPTP EGSPILKRKL GVDGE EEEP PPEPEPEPEP EPEKADTENG EKEVPEPPPE PPKKTPPPPP PKKEEAGGAG LEEFWGELEV QRVKFLNYLS RNFYTL RFL ALFLAFAINF ILLFYKVSDS PPGEDDIEGS GAGDMSGAGS GDGSGWGSRA GEEVEGDEDE NMVYYFLEES TGYMEPA LR CLSLLHTLVA FLCIIGYNCL KVPLVIFKRE KELARKLEFD GLYITEQPED DDVKGQWDRL VLNTPSFPSN YWDKFVKR K VLDKHGDIFG RERIAELLGM DLASLEITAH NERKPDPPPG LLTWIMSIDV KYQIWKFGVI FTDNSFLYLG WYMVMSLLG HYNNFFFAAH LLDIAMGVKT LRTILSSVTH NGKQLVMTVG LLAVVVYLYT VVAFNFFRKF YNKSEDEDEP DMKCDDMMTC YLFHMYVGV RAGGGIGDEI EDPAGDEYEL YRVVFDITFF FFVIVILLAI IQGLIIDAFG ELRDQQEQVK EDMETKCFIC G IGSDYFDT TPHGFETHTL EEHNLANYMF FLMYLINKDE TEHTGQESYV WKMYQERCWD FFPAGDCFRK QYEDQLS UniProtKB: Ryanodine receptor 1 |
-分子 #2: Peptidyl-prolyl cis-trans isomerase FKBP1A
分子 | 名称: Peptidyl-prolyl cis-trans isomerase FKBP1A / タイプ: protein_or_peptide / ID: 2 / コピー数: 4 / 光学異性体: LEVO / EC番号: peptidylprolyl isomerase |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 11.939629 KDa |
配列 | 文字列: MGVQVETISP GDGRTFPKRG QTCVVHYTGM LEDGKKFDSS RDRNKPFKFT LGKQEVIRGW EEGVAQMSVG QRAKLIISSD YAYGATGHP GIIPPHATLV FDVELLKLE UniProtKB: Peptidyl-prolyl cis-trans isomerase FKBP1A |
-分子 #3: Protein S100A1
分子 | 名称: Protein S100A1 / タイプ: protein_or_peptide / ID: 3 / コピー数: 8 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 10.516784 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGSELESAME TLINVFHAHS GKEGDKYKLS KKELKDLLQT ELSGFLDVQK DADAVDKVMK ELDENGDGEV DFKEYVVLVA ALTVACNNF FWETS UniProtKB: Protein S100 |
-分子 #4: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 4 / コピー数: 4 / 式: ZN |
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分子量 | 理論値: 65.409 Da |
-分子 #5: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
分子 | 名称: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / タイプ: ligand / ID: 5 / コピー数: 8 / 式: PCW |
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分子量 | 理論値: 787.121 Da |
Chemical component information | ![]() ChemComp-PCW: |
-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 | 8.5 mg/mL | |||||||||||||||||||||
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緩衝液 | pH: 7.4 構成要素:
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グリッド | モデル: Quantifoil R0.6/1 / 材質: GOLD / メッシュ: 300 | |||||||||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277.15 K / 装置: FEI VITROBOT MARK IV | |||||||||||||||||||||
詳細 | 0.15 mmol/L S100A1-dimer |
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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 K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 12147 / 平均電子線量: 58.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 100.0 µm / 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): 1.2 µm / 最小 デフォーカス(公称値): 0.5 µm |
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 |
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画像解析
初期モデル | モデルのタイプ: INSILICO MODEL / In silico モデル: CryoSPARC ab initio |
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最終 再構成 | 想定した対称性 - 点群: C4 (4回回転対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.21 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: cryoSPARC / 使用した粒子像数: 36506 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: cryoSPARC / 詳細: CryoSPARC branch-and-bound |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: cryoSPARC / 詳細: CryoSPARC branch-and-bound |