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基本情報
登録情報 | データベース: EMDB / ID: EMD-9825 | |||||||||
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タイトル | Structure of RyR2 (F/A/Ca2+ dataset) | |||||||||
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![]() | cryo-EM / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of calcium-mediated signaling / negative regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of release of sequestered calcium ion into cytosol / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus / response to redox state / protein maturation by protein folding / 'de novo' protein folding ...positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of calcium-mediated signaling / negative regulation of insulin secretion involved in cellular response to glucose stimulus / negative regulation of release of sequestered calcium ion into cytosol / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus / response to redox state / protein maturation by protein folding / 'de novo' protein folding / negative regulation of heart rate / FK506 binding / positive regulation of axon regeneration / channel regulator activity / smooth muscle contraction / response to vitamin E / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / calcium channel inhibitor activity / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / T cell proliferation / release of sequestered calcium ion into cytosol / Ion homeostasis / regulation of cytosolic calcium ion concentration / sarcoplasmic reticulum membrane / calcium channel complex / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / calcium-mediated signaling / response to hydrogen peroxide / Stimuli-sensing channels / Z disc / positive regulation of cytosolic calcium ion concentration / protein refolding / transmembrane transporter binding / signaling receptor binding / membrane / cytosol / cytoplasm 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: 4.8 Å | |||||||||
![]() | Chi XM / Gong DS | |||||||||
![]() | ![]() タイトル: Molecular basis for allosteric regulation of the type 2 ryanodine receptor channel gating by key modulators. 著者: Ximin Chi / Deshun Gong / Kang Ren / Gewei Zhou / Gaoxingyu Huang / Jianlin Lei / Qiang Zhou / Nieng Yan / ![]() ![]() 要旨: The type 2 ryanodine receptor (RyR2) is responsible for releasing Ca from the sarcoplasmic reticulum of cardiomyocytes, subsequently leading to muscle contraction. Here, we report 4 cryo-electron ...The type 2 ryanodine receptor (RyR2) is responsible for releasing Ca from the sarcoplasmic reticulum of cardiomyocytes, subsequently leading to muscle contraction. Here, we report 4 cryo-electron microscopy (cryo-EM) structures of porcine RyR2 bound to distinct modulators that, together with our published structures, provide mechanistic insight into RyR2 regulation. Ca alone induces a contraction of the central domain that facilitates the dilation of the S6 bundle but is insufficient to open the pore. The small-molecule agonist PCB95 helps Ca to overcome the barrier for opening. FKBP12.6 induces a relaxation of the central domain that decouples it from the S6 bundle, stabilizing RyR2 in a closed state even in the presence of Ca and PCB95. Although the channel is open when PCB95 is replaced by caffeine and adenosine 5'-triphosphate (ATP), neither of the modulators alone can sufficiently counter the antagonistic effect to open the channel. Our study marks an important step toward mechanistic understanding of the sophisticated regulation of this key channel whose aberrant activity engenders life-threatening cardiac disorders. | |||||||||
履歴 |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 226.7 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 15.5 KB 15.5 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 14.1 KB | 表示 | ![]() |
画像 | ![]() | 351.5 KB | ||
Filedesc metadata | ![]() | 8.9 KB | ||
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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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ボクセルのサイズ | X=Y=Z: 1.30654 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
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試料の構成要素
-全体 : RyR2 in complex with FKBP12.6
全体 | 名称: RyR2 in complex with FKBP12.6 |
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要素 |
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-超分子 #1: RyR2 in complex with FKBP12.6
超分子 | 名称: RyR2 in complex with FKBP12.6 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
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由来(天然) | 生物種: ![]() ![]() |
-分子 #1: Peptidyl-prolyl cis-trans isomerase FKBP1B
分子 | 名称: Peptidyl-prolyl cis-trans isomerase FKBP1B / タイプ: protein_or_peptide / ID: 1 / 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: 11.798501 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGVEIETISP GDGRTFPKKG QTCVVHYTGM LQNGKKFDSS RDRNKPFKFR IGKQEVIKGF EEGAAQMSLG QRAKLTCTPD VAYGATGHP GVIPPNATLI FDVELLNLE UniProtKB: Peptidyl-prolyl cis-trans isomerase FKBP1B |
-分子 #2: RyR2
分子 | 名称: RyR2 / タイプ: protein_or_peptide / ID: 2 / 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: 564.905625 KDa |
配列 | 文字列: MADGGEGEDE IQFLRTDDEV VLQCTATIHK EQQKLCLAAE GFGNRLCFLE STSNSKNVPP DLSICTFVLE QSLSVRALQE MLANTVEKS EGQVDVEKWK FMMKTAQGGG HRTLLYGHAI LLRHSYSGMY LCCLSTSRSS TDKLAFDVGL QEDTTGEACW W TIHPASKQ ...文字列: MADGGEGEDE IQFLRTDDEV VLQCTATIHK EQQKLCLAAE GFGNRLCFLE STSNSKNVPP DLSICTFVLE QSLSVRALQE MLANTVEKS EGQVDVEKWK FMMKTAQGGG HRTLLYGHAI LLRHSYSGMY LCCLSTSRSS TDKLAFDVGL QEDTTGEACW W TIHPASKQ RSEGEKVRVG DDLILVSVSS ERYLHLSYGN VSLHVDAAFQ QTLWSVAPIS SGSEAAQGYL IGGDVLRLLH GH MDECLTV PSGEHGEEQR RTVHYEGGAV SVHARSLWRL ETLRVAWSGS HIRWGQPFRL RHVTTGKYLS LMEDKSLLLM DKE KADVKS TAFTFRSSKE KLDVGVRKEV DGMGTSEIKY GDSVCFIQHI GTGLWLTYQS VDVKSVRMGS IQRKAIMHHE GHMD DGLNL SRSQHEESRT ARVIRSTVFL FNRFIRGLDA LSKKAKASTV DLPIESVSLS LQDLIGYFHP PDEHLEHEDK QNRLR ALKN RQNLFQEEGM INLVLECIDR LHVYSSAAHF ADVAGREAGE SWKSILNSLY ELLAALIRGN RKNCAQFSGS LDWLIS RLE RLEASSGILE VLHCVLVESP EALNIIKEGH IKSIISLLDK HGRNHKVLDV LCSLCVCHGV AVRSNQHLIC DNLLPGR DL LLQTRLVNHV SSMRPNIFLG VSEGSAQYKK WYYELMVDHT EPFVTAEATH LRVGWASTEG YSPYPGGGEE WGGNGVGD D LFSYGFDGLH LWSGCIARTV SSPNQHLLRT DDVISCCLDL SAPSISFRIN GQPVQGMFEN FNIDGLFFPV VSFSAGIKV RFLLGGRHGE FKFLPPPGYA PCYEAVLPKE KLKVEHSREY KQERTYTRDL LGPTVSLTQA AFTPIPVDTS QIVLPPHLER IREKLAENI HELWVMNKIE LGWQYGPVRD DNKRQHPCLV EFSKLPEQER NYNLQMSLET LKTLLALGCH VGISDEHAEE K VKKMKLPK NYQLTSGYKP APMDLSFIKL TPSQEAMVDK LAENAHNVWA RDRIRQGWTY GIQQDVKNRR NPRLVPYALL DD RTKKSNK DSLREAVRTL LGYGYNLEAP DQDHAARAEV CSGTGERFRI FRAEKTYAVK AGRWYFEFEA VTAGDMRVGW SRP GCQPDQ ELGSDERAFA FDGFKAQRWH QGNEHYGRSW QAGDVVGCMV DMTEHTMMFT LNGEILLDDS GSELAFKDFD VGDG FIPVC SLGVAQVGRM NFGKDVSTLK YFTICGLQEG YEPFAVNTNR DITMWLSKRL PQFLQVPSSH EHIEVTRIDG TIDSS PCLK VTQKSFGSQN SSTDIMFYRL SMPIECAEVF SKTSAGGIPG ASLFGPKNDL EDYDADSDFE VLMKTAHGHL VPDRVD KDK EATKPEFNNH KDYAQEKPSR LKQRFLLRRT KPDYSTSHSA RLTEDVLADD RDDYDYLMQT STYYYSVRIF PGQEPAN VW VGWITSDFHQ YDTAFDLDRV RTVTVTLGDE KGKVHESIKR SNCYMVCAGE SMSPGQGRNN NGLEIGCVVD AASGLLTF T ANGKDLSTYY QVEPSTKLFP AVFAQATSPN VFQFELGRIK NVMPLSAGLF KSEHKNPVPQ CPPRLHVQFL SHVLWSRMP NQFLKVDVSR ISERQGWLVQ CLEPLQFMSL HIPEENRSVD ILELTEQEEL LKFHYHTLRL YSAVCALGNH RVAHALCSHV DEPQLLYAI ENKYMPGLLR AGYYDLLIDI HLSSYATARL MMNNEFIVPM TEETKSITLF PDENKKHGLP GIGLSTSLRP R MQFSSPSF VSINNECYQY SPEFPLDILK AKTIQMLTEA VQEGSLHARD PVGGTTEFLF VPLIKLFYTL LIMGIFHNED LK HILQLIE PSVFKEAAGP EEESDTLEKE PCASEDSRLE GPAEEESKGG KRPKEGLLQM KLPEPVKLQM CLLLQYLCDC QVR HRIEAI VAFSDDFVAK LQDNQRFRYN EVMQALNMSA ALTARKTKEF RSPPQEQINM LLNFKDDKSE CPCPEEIRDQ LLDF HEDLM THCGIELDED GSLDGNSDLT IRGRLLSLVE KVTYLKKKQA EKLVESDSKK SSTLQQLISE TMVRWAQESV IEDPE LVRA MFVLLHRQYD GIGGLVRALP KTYTINGVSV EDTINLLASL GQIRSLLSVR MGKEEEKLMI RGLGDIMNNK VFYQHP NLM RALGMHETVM EVMVNVLGGG ESKEITFPKM VANCCRFLCY FCRISRQNQK AMFDHLSYLL ENSSVGLASP AMRGSTP LD VAAASVMDNN ELALALREPD LEKVVRYLAG CGLQSCQMLV SKGYPDIGWN PVEGERYLDF LRFAVFCNGE SVEENANV V VRLLIRRPEC FGPALRGEGG NGLLAAMEEA IKIAEDPSRD GPSPTSGSSK MPDTEGEEDD TIHMGNAIMT FYAALIDLL GRCAPEMHLI HAAKGEAIRI RSILRSLIPL GDLVGVISIA FQMPTIAKDG NVVEPDMSAG FCPDHKAAMV LFLDRVYGIE VQDFLLHLL EVGFLPDLRA AASLDTAALS ATDMALALNR YLCTAVLPLL TRCAPLFAGT EHHASLIDSL LHTVYRLSKG C SLTKAQRD SIEVCLLSIC GQLRPSMMQH LLRRLVFDVP LLNEHAKMPL KLLTNHYERC WKYYCLPGGW GNFGAASEEE LH LSRKLFW GIFDALSQKK YEQELFKLAL PCLSAVAGAL PPDYMESNYV SMMEKQSSMD SEGNFNPQPV DTSNITIPEK LEY FINKYA EHSHDKWSMD KLANGWIYGE IYSDSSKVQP LMKPYKLLSE KEKEIYRWPI KESLKTMLAW GWRIERTREG DSMA LYNRT RRISQTSQVS VDAAHGYSPR AIDMSNVTLS RDLHAMAEMM AENYHNIWAK KKKLELESKG GGNHPLLVPY DTLTA KEKA KDREKAQDIL KFLQINGYAV SRGFKDLELD TPSIEKRFAY SFLQQLIRYV DEAHQYILEF DGGSRSKGEH FPYEQE IKF FAKVVLPLID QYFKNHRLYF LSAASRPLCS GGHASNKEKE MVTSLFCKLG VLVRHRISLF GNDATSIVNC LHILGQT LD ARTVMKTGLE SVKSALRAFL DNAAEDLEKT MENLKQGQFT HTRNQPKGVT QIINYTTVAL LPMLSSLFEH IGQHQFGE D LILEDVQVSC YRILTSLYAL GTSKSIYVER QRSALGECLA AFAGAFPVAF LETHLDKHNI YSIYNTKSSR ERAALNLPT NVEDVCPNIP SLEKLMEEIV DLAESGIRYT QMPHVMEVVL PMLCSYMSRW WEHGPENNPG RAEMCCTALN SEHMNTLLGN ILKIIYNNL GIDEGAWMKR LAVFSQPIIN KVKPQLLKTH FLPLMEKLKK KAAMVVSEED HLKSEVRGDM SEAELLILDE F TTLARDLY AFYPLLIRFV DYNRAKWLKE PNPEAEDLFR MVAEVFIYWS KSHNFKREEQ NFVVQNEINN MSFLITDTKS KM SKAAVSD QERKKMKRKG DRYSMQTSLI VAALKRLLPI GLNICAPGDQ ELIALAKNRF SLKDTEDEVR DIIRSNIHLQ GKL EDPAIR WQMALYKDLP NRTEDTSDPE KTVERVLDIA NVLFHLEQKS TCMRRRYYSL VEHPQRSKKA VWHKLLSKQR KRAV VACFR MAPLYNLPRH RAVNLFLQGY EKSWIETEEH YFEDKLIEDL AKPGAVPPEE DEGTKRVDPL HQLILLFSRT ALTEK CKLE EDFLYMAYAD IMAKSCHDEE DDDGEEEVKS FEEKEMEKQK LLYQQARLHD RGAAEMVLQT ISASKGETGP MVAATL KLG IAILNGGNST VQQKMLEYLK EKKDVGFFQS LAGLMQSCSV LDLNAFERQN KAEGLGMVTE EGSGEKVLQD DEFTCDL FR FLQLLCEGHN SDFQNYLRTQ TGNNTTVNII ISTVDYLLRV QESISDFYWY YSGKDVIDEQ GQRNFSKAIQ VAKQVFNT L TEYIQGPCTG NQQSLAHSRL WDAVVGFLHV FAHMQMKLSQ DSSQIELLKE LMDLQKDMVV MLLSMLEGNV VNGTIGKQM VDMLVESSNN VEMILKFFDM FLKLKDLTSS DTFKEYDPDG KGVISKRDFH KAMESHKHYT QSETEFLLSC AETDENETLD YEEFVKRFH EPAKDIGFNV AVLLTNLSEH MPNDTRLQTF LELAESVLNY FQPFLGRIEI MGSAKRIERV YFEISESSRT Q WEKPQVKE SKRQFIFDVV NEGGEKEKME LFVNFCEDTI FEMQLAAQIS ESDLNERSAN KEESEKEKPE EQGPRMGFFS LV TVRSALL ALRYNVLTLM RMLSLKSLKK QMKKVKKMTV RDMVTAFFTS YWSVFMTLLH FAASVSRGFS RIIGGLLLGG SLV EGAKKI KVAELLANMP DPTQDEVRGD GDEGERKVLE GTLPSEDLTD LKELTEESDL LSDIFGLDLK REGGQYKLIP HNPN AGLSD LMSSPAPIPE VQEKFQEQKA KEEEKEEKEE NKSEPEKAEG EDGEKEEKAK EDKGKQKLRQ LHTHRYGEPE VPESA FWKK IIAYQQKLLN YFARNFYNMR MLALFVAFAI NFILLFYKVS TSSVVEGKEL PTRSSSENAN FGSLDSSSPR IIAVHY VLE ESSGYMEPTL RILAILHTVI SFFCIIGYYC LKVPLVIFKR EKEVARKLEF DGLYITEQPS EDDIKGQWDR LVINTQS FP NNYWDKFVKR KVMDKYGEFY GRDRISELLG MDKAALDFSD AREKKKPKKD SSLSAVLNSI DVKYQMWKLG VVFTDNSF L YLAWYMTMSV LGHYNNFFFA AHLLDIAMGF KTLRTILSSV THNGKQLVLT VGLLAVVVYL YTVVAFNFFR KFYNKSEDG DTPDMKCDDM LTCYMFHMYV GVRAGGGIGD EIEDPAGDEY EIYRIIFDIT FFFFVIVILL AIIQGLIIDA FGELRDQQEQ VKEDMETKC FICGIGNDYF DTVPHGFETH TLQEHNLANY LFFLMYLINK DETEHTGQES YVWKMYQERC WEFFPAGDCF R KQYEDQLN |
-分子 #3: ADENOSINE-5'-TRIPHOSPHATE
分子 | 名称: ADENOSINE-5'-TRIPHOSPHATE / タイプ: ligand / ID: 3 / コピー数: 4 / 式: ATP |
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分子量 | 理論値: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-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 |
-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
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
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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) 平均電子線量: 48.6 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 |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |