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Structure paper

TitleStructural identification of the RY12 domain of RyR1 as an ADP sensor and the target of the malignant hyperthermia therapeutic dantrolene
Journal, issue, pagesNat Commun, Year 2026
Publish dateDec 4, 2025 (structure data deposition date)
AuthorsKim K / Li H / Yuan Q / Melville Z / Zalk R / des Georges A / Frank J / Hendrickson WA / Marks AR / Clarke OB
External linksNat Commun / Search PubMed
MethodsEM (single particle)
Resolution1.99 - 3.18 Å
Structure data

EMDB-74282: Consensus map of rabbit RyR1 complexed with FKBP12.6, calmodulin, ATP, and 4-chloro-m-cresol
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-74290: Focused map of rabbit RyR1 complexed with FKBP12.6, calmodulin, ATP, and 4-chloro-m-cresol (NSol mask)
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-74292: Focused map of rabbit RyR1 complexed with FKBP12.6, calmodulin, ATP, and 4-chloro-m-cresol (BSol mask)
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-74293: Focused map of rabbit RyR1 complexed with FKBP12.6, calmodulin, ATP, and 4-chloro-m-cresol (Core-Pore mask)
Method: EM (single particle) / Resolution: 2.53 Å

EMDB-74294: Focused map of rabbit RyR1 complexed with FKBP12.6, calmodulin, ATP, and 4-chloro-m-cresol (JSol mask)
Method: EM (single particle) / Resolution: 2.48 Å

EMDB-74295: Consensus map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ADP, 4-chloro-m-cresol, caffeine, and Mg2+
Method: EM (single particle) / Resolution: 2.37 Å

EMDB-74296: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ADP, 4-chloro-m-cresol, caffeine, and Mg2+ (NSol mask)
Method: EM (single particle) / Resolution: 2.2 Å

EMDB-74297: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ADP, 4-chloro-m-cresol, caffeine, and Mg2+ (JSol mask)
Method: EM (single particle) / Resolution: 2.25 Å

EMDB-74298: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ADP, 4-chloro-m-cresol, caffeine, and Mg2+ (BSol mask)
Method: EM (single particle) / Resolution: 2.42 Å

EMDB-74299: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ADP, 4-chloro-m-cresol, caffeine, and Mg2+ (Core-Pore mask)
Method: EM (single particle) / Resolution: 2.18 Å

EMDB-74300: Consensus map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ATP, 4-chloro-m-cresol, caffeine, and Mg2+
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-74301: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ATP, 4-chloro-m-cresol, caffeine, and Mg2+ (NSol mask)
Method: EM (single particle) / Resolution: 2.76 Å

EMDB-74302: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ATP, 4-chloro-m-cresol, caffeine, and Mg2+ (JSol mask)
Method: EM (single particle) / Resolution: 2.72 Å

EMDB-74303: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ATP, 4-chloro-m-cresol, caffeine, and Mg2+ (BSol mask)
Method: EM (single particle) / Resolution: 2.95 Å

EMDB-74304: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ATP, 4-chloro-m-cresol, caffeine, and Mg2+ (Core-Pore mask)
Method: EM (single particle) / Resolution: 2.75 Å

EMDB-74305: Consensus map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ADP, 4-chloro-m-cresol, caffeine, and Mg2+
Method: EM (single particle) / Resolution: 2.58 Å

EMDB-74306: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ADP, 4-chloro-m-cresol, caffeine, and Mg2+ (NSol mask)
Method: EM (single particle) / Resolution: 2.29 Å

EMDB-74307: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ADP, 4-chloro-m-cresol, caffeine, and Mg2+ (JSol mask)
Method: EM (single particle) / Resolution: 2.32 Å

EMDB-74308: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ADP, 4-chloro-m-cresol, caffeine, and Mg2+ (BSol mask)
Method: EM (single particle) / Resolution: 2.34 Å

EMDB-74309: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ADP, 4-chloro-m-cresol, caffeine, and Mg2+ (Core-Pore mask)
Method: EM (single particle) / Resolution: 2.34 Å

EMDB-74310: Focused map of corner subparticles of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking muscle fatigue; Corner mask)
Method: EM (single particle) / Resolution: 1.99 Å

EMDB-74311: Consensus map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking muscle fatigue)
Method: EM (single particle) / Resolution: 2.23 Å

EMDB-74314: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking muscle fatigue) (NSol mask)
Method: EM (single particle) / Resolution: 2.07 Å

EMDB-74328: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking muscle fatigue; JSol mask)
Method: EM (single particle) / Resolution: 2.11 Å

EMDB-74348: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking physiological conditions; NSol mask)
Method: EM (single particle) / Resolution: 2.57 Å

EMDB-74349: Consensus map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking physiological conditions)
Method: EM (single particle) / Resolution: 2.57 Å

EMDB-74350: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking muscle fatigue; BSol mask)
Method: EM (single particle) / Resolution: 2.32 Å

EMDB-74351: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking muscle fatigue; Core-Pore mask)
Method: EM (single particle) / Resolution: 2.09 Å

EMDB-74352: Focused map of corner subparticles of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking physiological conditions; Corner mask)
Method: EM (single particle) / Resolution: 2.26 Å

74353

9zk8

EMDB-74353, PDB-9zk8:
Structure of RY12 domain of rabbit RyR1 complexed with ADP and Mg2+ (mimicking physiological conditions; bound and closed RY12)
Method: EM (single particle) / Resolution: 3.18 Å

EMDB-74354: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking physiological conditions; JSol mask)
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-74355: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking physiological conditions; BSol mask)
Method: EM (single particle) / Resolution: 2.66 Å

EMDB-74356: Consensus map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene and Mg2+
Method: EM (single particle) / Resolution: 2.96 Å

74357

9zk9

EMDB-74357: Focused map of RY12 domain of rabbit RyR1 in the presence of dantrolene and Mg2+ (open RY12 conformation)
PDB-9zk9: Structure of RY12 domain of rabbit RyR1 in the presence of dantrolene and Mg2+ (open RY12 conformation)
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-74358: Consensus map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, Mg2+, and Ca2+
Method: EM (single particle) / Resolution: 2.55 Å

74359

9zka

EMDB-74359, PDB-9zka:
Structure of RY12 domain of rabbit RyR1 in the presence of ATP, Mg2+, and Ca2+ (open RY12 conformation)
Method: EM (single particle) / Resolution: 2.64 Å

EMDB-74361: Focused map of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking physiological conditions; Core-Pore mask)
Method: EM (single particle) / Resolution: 2.4 Å

74362

9zkc

EMDB-74362, PDB-9zkc:
Structure of RY12 domain of rabbit RyR1 in the presence of ATP, ADP, and Mg2+ (mimicking physiological conditions; unbound and open RY12)
Method: EM (single particle) / Resolution: 2.66 Å

EMDB-74363: Consensus map of rabbit RyR1 complexed with FKBP12 and calmodulin in the presence of ARM210, ATP, caffeine, and Ca2+
Method: EM (single particle) / Resolution: 2.39 Å

74364

9zkd

EMDB-74364: Focused map of RY12 domain of rabbit RyR1 complexed with ADP and Mg2+ (mimicking muscle fatigue)
PDB-9zkd: Structure of RY12 domain of rabbit RyR1 complexed with ADP and Mg2+ (mimicking muscle fatigue)
Method: EM (single particle) / Resolution: 2.32 Å

74365

9zke

EMDB-74365, PDB-9zke:
Structure of RY12 domain of rabbit RyR1 complexed with ARM210 and ATP
Method: EM (single particle) / Resolution: 2.96 Å

EMDB-74392: Focused map of corner subparticles of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, 4-chloro-m-cresol, and caffeine (Corner mask)
Method: EM (single particle) / Resolution: 2.39 Å

74394

9zl7

EMDB-74394, PDB-9zl7:
Structure of RY12 domain of rabbit RyR1 complexed with ATP and 4-chloro-m-cresol
Method: EM (single particle) / Resolution: 2.77 Å

EMDB-74397: Focused map of corner subparticles of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ADP, 4-chloro-m-cresol, caffeine, and Mg2+ (Corner mask)
Method: EM (single particle) / Resolution: 2.08 Å

74398

9zlc

EMDB-74398: Focused map of rabbit RyR1 RY12 domain complexed with ADP and Mg2+
PDB-9zlc: Structure of rabbit RyR1 RY12 domain complexed with ADP and Mg2+
Method: EM (single particle) / Resolution: 2.52 Å

EMDB-74401: Focused map of corner subparticles of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ATP, 4-chloro-m-cresol, caffeine, and Mg2+ (Corner mask)
Method: EM (single particle) / Resolution: 2.49 Å

74402

9zlf

EMDB-74402, PDB-9zlf:
Structure of RY12 domain of rabbit RyR1 complexed with dantrolene and ATP
Method: EM (single particle) / Resolution: 2.71 Å

74403

9zlh

EMDB-74403, PDB-9zlh:
Structure of RY12 domain of rabbit RyR1 complexed with dantrolene and ADP
Method: EM (single particle) / Resolution: 2.14 Å

EMDB-74404: Focused map of corner subparticles of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ADP, 4-chloro-m-cresol, caffeine, and Mg2+ (Corner mask)
Method: EM (single particle) / Resolution: 2.16 Å

74436

9zn6

EMDB-74436, PDB-9zn6:
Structure of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ADP, 4-chloro-m-cresol, caffeine, and Mg2+
Method: EM (single particle) / Resolution: 2.58 Å

74437

9zn7

EMDB-74437, PDB-9zn7:
Structure of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking muscle fatigue)
Method: EM (single particle) / Resolution: 2.23 Å

74438

9zn8

EMDB-74438, PDB-9zn8:
Structure of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of ATP, ADP, and Mg2+ (mimicking physiological conditions)
Method: EM (single particle) / Resolution: 2.57 Å

74439

9zn9

EMDB-74439, PDB-9zn9:
Structure of rabbit RyR1 complexed with FKBP12.6, calmodulin, ATP, 4-chloro-m-cresol, and caffeine
Method: EM (single particle) / Resolution: 2.77 Å

74441

9zna

EMDB-74441, PDB-9zna:
Structure of rabbit RyR1 complexed with FKBP12.6, calmodulin, ADP, 4-chloro-m-cresol, caffeine, and Mg2+
Method: EM (single particle) / Resolution: 2.37 Å

74445

9znd

EMDB-74445, PDB-9znd:
Structure of rabbit RyR1 complexed with FKBP12.6 and calmodulin in the presence of dantrolene, ATP, 4-chloro-m-cresol, caffeine, and Mg2+
Method: EM (single particle) / Resolution: 3.09 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-KVR:
4-[(7-methoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)methyl]benzoic acid

ChemComp-43M:
4-CHLORO-3-METHYLPHENOL


ChemComp, No image

ChemComp-U1C:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-CA:
Unknown entry

ChemComp-CFF:
CAFFEINE / medication*YM

ChemComp-PLC:
DIUNDECYL PHOSPHATIDYL CHOLINE / phospholipid*YM

ChemComp-CPS:
3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE / detergent*YM

Source
  • oryctolagus cuniculus (rabbit)
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / sarcoplasmic reticulum / intracellular calcium channel / excitation-contraction coupling / complex

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