Cryo-EM Structure of Ryanodine Receptor 1: Drug Bound Open Conformation Composite Map

2026-01-28 REL RCSB INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY RCSB RCSB 2025-05-12 2026-01-28 2026-01-28 2026-01-28 Canadian Institutes of Health Research (CIHR) Canada Cryo-EM Structure of Ryanodine Receptor 1: Drug Bound Open Conformation Composite Map Molinarolo SM Van Petegem F Ion channel, Calcium Channel, TRANSPORT PROTEIN, TRANSPORT PROTEIN-Isomerase complex Molinarolo S Valdivia CR Valdivia HH Van Petegem F Cryo-electron microscopy reveals sequential binding and activation of Ryanodine Receptors by statin triplets. Nat Commun UK 16 11508 11508 2025 41266329 doi:10.1038/s41467-025-66522-0 2041-1723 EMD-70584 consensus EM volume

Consensus

EMD-70585 focused EM volume

N-terminal Focus

EMD-70586 focused EM volume

BSol Focus

EMD-70587 focused EM volume

C-terminal Focus

EMD-70588 focused EM volume

Transmembrane Focus

9ol4 FULLOVERLAP EMDB EMD-70584 consensus EM volume

Consensus

EMDB EMD-70585 focused EM volume

N-terminal Focus

EMDB EMD-70586 focused EM volume

BSol Focus

EMDB EMD-70587 focused EM volume

C-terminal Focus

EMDB EMD-70588 focused EM volume

Transmembrane Focus

EMDB EMD-70589 associated EM volume

Cryo-EM Structure of Ryanodine Receptor 1: Drug Bound Open Conformation

Tetrameric complex of RyR1 with FKBP12.6 Tetrameric complex of RyR1 with FKBP12.6 0 1 2 Oryctolagus cuniculus 2.39 Ryanodine receptor 1 Oryctolagus cuniculus 0.5659086249999999 4 LEVO MGDGGEGEDEVQFLRTDDEVVLQCSATVLKEQLKLCLAAEGFGNRLCFLEPTSNAQNVPPDLAICCFTLEQSLSVRALQE MLANTVEAGVESSQGGGHRTLLYGHAILLRHAHSRMYLSCLTTSRSMTDKLAFDVGLQEDATGEACWWTMHPASKQRSEG EKVRVGDDLILVSVSSERYLHLSTASGELQVDASFMQTLWNMNPICSCCEEGYVTGGHVLRLFHGHMDECLTISAADSDD QRRLVYYEGGAVCTHARSLWRLEPLRISWSGSHLRWGQPLRIRHVTTGRYLALTEDQGLVVVDACKAHTKATSFCFRVSK EKLDTAPKRDVEGMGPPEIKYGESLCFVQHVASGLWLTYAAPDPKALRLGVLKKKAILHQEGHMDDALFLTRCQQEESQA ARMIHSTAGLYNQFIKGLDSFSGKPRGSGPPAGPALPIEAVILSLQDLIGYFEPPSEELQHEEKQSKLRSLRNRQSLFQE EGMLSLVLNCIDRLNVYTTAAHFAEYAGEEAAESWKEIVNLLYELLASLIRGNRANCALFSTNLDWVVSKLDRLEASSGI LEVLYCVLIESPEVLNIIQENHIKSIISLLDKHGRNHKVLDVLCSLCVCNGVAVRSNQDLITENLLPGRELLLQTNLINY VTSIRPNIFVGRAEGSTQYGKWYFEVMVDEVVPFLTAQATHLRVGWALTEGYSPYPGGGEGWGGNGVGDDLYSYGFDGLH LWTGHVARPVTSPGQHLLAPEDVVSCCLDLSVPSISFRINGCPVQGVFEAFNLDGLFFPVVSFSAGVKVRFLLGGRHGEF KFLPPPGYAPCHEAVLPRERLRLEPIKEYRREGPRGPHLVGPSRCLSHTDFVPCPVDTVQIVLPPHLERIREKLAENIHE LWALTRIEQGWTYGPVRDDNKRLHPCLVNFHSLPEPERNYNLQMSGETLKTLLALGCHVGMADEKAEDNLKKTKLPKTYM MSNGYKPAPLDLSHVRLTPAQTTLVDRLAENGHNVWARDRVAQGWSYSAVQDIPARRNPRLVPYRLLDEATKRSNRDSLC QAVRTLLGYGYNIEPPDQEPSQVENQSRWDRVRIFRAEKSYTVQSGRWYFEFEAVTTGEMRVGWARPELRPDVELGADEL AYVFNGHRGQRWHLGSEPFGRPWQSGDVVGCMIDLTENTIIFTLNGEVLMSDSGSETAFREIEIGDGFLPVCSLGPGQVG HLNLGQDVSSLRFFAICGLQEGFEPFAINMQRPVTTWFSKSLPQFEPVPPEHPHYEVARMDGTVDTPPCLRLAHRTWGSQ NSLVEMLFLRLSLPVQFHQHFRCTAGATPLAPPGLQPPAEDEARAAEPDPDYENLRRSAGGWGEAEGGKEGTAKEGTPGG TPQPGVEAQPVRAENEKDATTEKNKKRGFLFKAKKAAMMTQPPATPALPRLPHDVVPADNRDDPEIILNTTTYYYSVRVF AGQEPSCVWVGWVTPDYHQHDMNFDLSKVRAVTVTMGDEQGNVHSSLKCSNCYMVWGGDFVSPGQQGRISHTDLVIGCLV DLATGLMTFTANGKESNTFFQVEPNTKLFPAVFVLPTHQNVIQFELGKQKNIMPLSAAMFLSERKNPAPQCPPRLEVQML MPVSWSRMPNHFLQVETRRAGERLGWAVQCQDPLTMMALHIPEENRCMDILELSERLDLQRFHSHTLRLYRAVCALGNNR VAHALCSHVDQAQLLHALEDAHLPGPLRAGYYDLLISIHLESACRSRRSMLSEYIVPLTPETRAITLFPPGRKGGNARRH GLPGVGVTTSLRPPHHFSPPCFVAALPAAGVAEAPARLSPAIPLEALRDKALRMLGEAVRDGGQHARDPVGGSVEFQFVP VLKLVSTLLVMGIFGDEDVKQILKMIEPEVFTEEEEEEEEEEEEEEEEEEDEEEKEEDEEEEEKEDAEKEEEEAPEGEKE DLEEGLLQMKLPESVKLQMCNLLEYFCDQELQHRVESLAAFAERYVDKLQANQRSRYALLMRAFTMSAAETARRTREFRS PPQEQINMLLHFKDEADEEDCPLPEDIRQDLQDFHQDLLAHCGIQLEGEEEEPEEETSLSSRLRSLLETVRLVKKKEEKP EEELPAEEKKPQSLQELVSHMVVRWAQEDYVQSPELVRAMFSLLHRQYDGLGELLRALPRAYTISPSSVEDTMSLLECLG QIRSLLIVQMGPQEENLMIQSIGNIMNNKVFYQHPNLMRALGMHETVMEVMVNVLGGGETKEIRFPKMVTSCCRFLCYFC RISRQNQRSMFDHLSYLLENSGIGLGMQGSTPLDVAAASVIDNNELALALQEQDLEKVVSYLAGCGLQSCPMLLAKGYPD IGWNPCGGERYLDFLRFAVFVNGESVEENANVVVRLLIRKPECFGPALRGEGGSGLLAAIEEAIRISEDPARDGPGVRRD RRREHFGEEPPEENRVHLGHAIMSFYAALIDLLGRCAPEMHLIQAGKGEALRIRAILRSLVPLDDLVGIISLPLQIPTLG KDGALVQPKMSASFVPDHKASMVLFLDRVYGIENQDFLLHVLDVGFLPDMRAAASLDTATFSTTEMALALNRYLCLAVLP LITKCAPLFAGTEHRAIMVDSMLHTVYRLSRGRSLTKAQRDVIEDCLMALCRYIRPSMLQHLLRRLVFDVPILNEFAKMP LKLLTNHYERCWKYYCLPTGWANFGVTSEEELHLTRKLFWGIFDSLAHKKYDQELYRMAMPCLCAIAGALPPDYVDASYS SKAEKKATVDAEGNFDPRPVETLNVIIPEKLDSFINKFAEYTHEKWAFDKIQNNWSYGENVDEELKTHPMLRPYKTFSEK DKEIYRWPIKESLKAMIAWEWTIEKAREGEEERTEKKKTRKISQTAQTYDPREGYNPQPPDLSGVTLSRELQAMAEQLAE NYHNTWGRKKKQELEAKGGGTHPLLVPYDTLTAKEKARDREKAQELLKFLQMNGYAVTRGLKDMELDTSSIEKRFAFGFL QQLLRWMDISQEFIAHLEAVVSSGRVEKSPHEQEIKFFAKILLPLINQYFTNHCLYFLSTPAKVLGSGGHASNKEKEMIT SLFCKLAALVRHRVSLFGTDAPAVVNCLHILARSLDARTVMKSGPEIVKAGLRSFFESASEDIEKMVENLRLGKVSQART QVKGVGQNLTYTTVALLPVLTTLFQHIAQHQFGDDVILDDVQVSCYRTLCSIYSLGTTKNTYVEKLRPALGECLARLAAA MPVAFLEPQLNEYNACSVYTTKSPRERAILGLPNSVEEMCPDIPVLDRLMADIGGLAESGARYTEMPHVIEITLPMLCSY LPRWWERGPEAPPPALPAGAPPPCTAVTSDHLNSLLGNILRIIVNNLGIDEATWMKRLAVFAQPIVSRARPELLHSHFIP TIGRLRKRAGKVVAEEEQLRLEAKAEAEEGELLVRDEFSVLCRDLYALYPLLIRYVDNNRAHWLTEPNANAEELFRMVGE IFIYWSKSHNFKREEQNFVVQNEINNMSFLTADSKSKMAKAGDAQSGGSDQERTKKKRRGDRYSVQTSLIVATLKKMLPI GLNMCAPTDQDLIMLAKTRYALKDTDEEVREFLQNNLHLQGKVEGSPSLRWQMALYRGLPGREEDADDPEKIVRRVQEVS AVLYHLEQTEHPYKSKKAVWHKLLSKQRRRAVVACFRMTPLYNLPTHRACNMFLESYKAAWILTEDHSFEDRMIDDLSKA GEQEEEEEEVEEKKPDPLHQLVLHFSRTALTEKSKLDEDYLYMAYADIMAKSCHLEEGGENGEAEEEEVEVSFEEKEMEK QRLLYQQSRLHTRGAAEMVLQMISACKGETGAMVSSTLKLGISILNGGNAEVQQKMLDYLKDKKEVGFFQSIQALMQTCS VLDLNAFERQNKAEGLGMVNEDGTVINRQNGEKVMADDEFTQDLFRFLQLLCEGHNNDFQNYLRTQTGNTTTINIIICTV DYLLRLQESISDFYWYYSGKDVIEEQGKRNFSKAMSVAKQVFNSLTEYIQGPCTGNQQSLAHSRLWDAVVGFLHVFAHMM MKLAQDSSQIELLKELLDLQKDMVVMLLSLLEGNVVNGMIARQMVDMLVESSSNVEMILKFFDMFLKLKDIVGSEAFQDY VTDPRGLISKKDFQKAMDSQKQFTGPEIQFLLSCSEADENEMINFEEFANRFQEPARDIGFNVAVLLTNLSEHVPHDPRL RNFLELAESILEYFRPYLGRIEIMGASRRIERIYFEISETNRAQWEMPQVKESKRQFIFDVVNEGGEAEKMELFVSFCED TIFEMQIAAQISEPEGEPEADEDEGMGEAAAEGAEEGAAGAEGAAGTVAAGATARLAAAAARALRGLSYRSLRRRVRRLR RLTAREAATALAALLWAVVARAGAAGAGAAAGALRLLWGSLFGGGLVEGAKKVTVTELLAGMPDPTSDEVHGEQPAGPGG DADGAGEGEGEGDAAEGDGDEEVAGHEAGPGGAEGVVAVADGGPFRPEGAGGLGDMGDTTPAEPPTPEGSPILKRKLGVD GEEEELVPEPEPEPEPEPEKADEENGEKEEVPEAPPEPPKKAPPSPPAKKEEAGGAGMEFWGELEVQRVKFLNYLSRNFY TLRFLALFLAFAINFILLFYKVSDSPPGEDDMEGSAAGDLAGAGSGGGSGWGSGAGEEAEGDEDENMVYYFLEESTGYME PALWCLSLLHTLVAFLCIIGYNCLKVPLVIFKREKELARKLEFDGLYITEQPGDDDVKGQWDRLVLNTPSFPSNYWDKFV KRKVLDKHGDIFGRERIAELLGMDLASLEITAHNERKPDPPPGLLTWLMSIDVKYQIWKFGVIFTDNSFLYLGWYMVMSL LGHYNNFFFAAHLLDIAMGVKTLRTILSSVTHNGKQLVMTVGLLAVVVYLYTVVAFNFFRKFYNKSEDEDEPDMKCDDMM TCYLFHMYVGVRAGGGIGDEIEDPAGDEYELYRVVFDITFFFFVIVILLAIIQGLIIDAFGELRDQQEQVKEDMETKCFI CGIGSDYFDTTPHGFETHTLEEHNLANYMFFLMYLINKDETEHTGQESYVWKMYQERCWDFFPAGDCFRKQYEDQLS P11716 Peptidyl-prolyl cis-trans isomerase FKBP1B Homo sapiens 0.012070758999999999 4 Escherichia coli LEVO SNAMGVEIETISPGDGRTFPKKGQTCVVHYTGMLQNGKKFDSSRDRNKPFKFRIGKQEVIKGFEEGAAQMSLGQRAKLTC TPDVAYGATGHPGVIPPNATLIFDVELLNLE P68106 5.2.1.8 CAFFEINE 0.000194191 4 CFF CALCIUM ION 4.0078e-05 4 CA 7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYRROL-1-YL]- 3,5-DIHYDROXY-HEPTANOIC ACID 0.00055864 12 117 ZINC ION 6.5409e-05 4 ZN singleParticle particle 10 7.5 10.0 Atorvastatin 2.0 DMSO 2.0 Caffeine 36.0 Free Ca2+ 2.0 EGTA 25.0 Tris 250.0 Sodium Chloride 0.1 TCEP 0.1 Benzamidine 0.375 CHAPS 0.001 DOPC Quantifoil R2/2 COPPER 300 CARBON HOLEY GLOW DISCHARGE 25 AIR 3.9e-05 ETHANE 100 277.15 FEI VITROBOT MARK IV TFS KRIOS FLOOD BEAM BRIGHT FIELD FIELD EMISSION GUN 300 0.5 2.5 FEI TITAN KRIOS AUTOGRID HOLDER NITROGEN TFS Selectris FEI FALCON IV (4k x 4k) 3 35751 50.0 1 PHASE FLIPPING AND AMPLITUDE CORRECTION 7TZC 3.37 FSC 0.143 CUT-OFF cryoSPARC 4.4.1 694588 MAXIMUM LIKELIHOOD MAXIMUM LIKELIHOOD emd_70589.map.gz 1 IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) 512 512 512 0 0 0 512 512 512 491.52 491.52 491.52 90.0 90.0 90.0 X Y Z 0.0 0.866438 0.003018884 0.021772817 0.96 0.96 0.96 0.123 AUTHOR ::::EMDATABANK.org::::EMD-70589:::: composite map 7TZC A 1-5037 PDB experimental model RIGID BODY FIT