Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural analyses of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment.
Journal, issue, pages	Sci Adv, Vol. 8, Issue 29, Page eabo1272, Year 2022
Publish date	Jul 22, 2022
Authors	Marco C Miotto / Gunnar Weninger / Haikel Dridi / Qi Yuan / Yang Liu / Anetta Wronska / Zephan Melville / Leah Sittenfeld / Steven Reiken / Andrew R Marks /
PubMed Abstract	Ryanodine receptor type 2 (RyR2) mutations have been linked to an inherited form of exercise-induced sudden cardiac death called catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT ...Ryanodine receptor type 2 (RyR2) mutations have been linked to an inherited form of exercise-induced sudden cardiac death called catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT results from stress-induced sarcoplasmic reticular Ca leak via the mutant RyR2 channels during diastole. We present atomic models of human wild-type (WT) RyR2 and the CPVT mutant RyR2-R2474S determined by cryo-electron microscopy with overall resolutions in the range of 2.6 to 3.6 Å, and reaching local resolutions of 2.25 Å, unprecedented for RyR2 channels. Under nonactivating conditions, the RyR2-R2474S channel is in a "primed" state between the closed and open states of WT RyR2, rendering it more sensitive to activation that results in stress-induced Ca leak. The Rycal drug ARM210 binds to RyR2-R2474S, reverting the primed state toward the closed state. Together, these studies provide a mechanism for CPVT and for the therapeutic actions of ARM210.
External links	Sci Adv / PubMed:35857850 / PubMed Central
Methods	EM (single particle)
Resolution	2.58 - 3.69 Å
Structure data	EMDB-26139: Structure of human RyR2 in the closed state. Method: EM (single particle) / Resolution: 3.53 Å 26405 7u9q EMDB-26405, PDB-7u9q: Structure of PKA phosphorylated human RyR2 in the closed state Method: EM (single particle) / Resolution: 3.11 Å 26407 7u9r EMDB-26407, PDB-7u9r: Structure of PKA phosphorylated human RyR2 in the open state Method: EM (single particle) / Resolution: 3.69 Å 26408 7u9t EMDB-26408, PDB-7u9t: Structure of PKA phosphorylated human RyR2 in the closed state in the presence of Calmodulin Method: EM (single particle) / Resolution: 2.68 Å 26409 7u9x EMDB-26409, PDB-7u9x: Structure of PKA phosphorylated human RyR2-R2474S in the closed state Method: EM (single particle) / Resolution: 2.58 Å 26410 7u9z EMDB-26410, PDB-7u9z: Structure of PKA phosphorylated human RyR2-R2474S in the open state Method: EM (single particle) / Resolution: 3.29 Å 26412 7ua1 EMDB-26412, PDB-7ua1: Structure of PKA phosphorylated human RyR2-R2474S in the closed state in the presence of ARM210 Method: EM (single particle) / Resolution: 2.99 Å 26413 7ua3 EMDB-26413, PDB-7ua3: Structure of PKA phosphorylated human RyR2-R2474S in the closed state in the presence of Calmodulin Method: EM (single particle) / Resolution: 2.97 Å 26414 7ua4 EMDB-26414, PDB-7ua4: Structure of PKA phosphorylated human RyR2-R2474S in the open state in the presence of Calmodulin Method: EM (single particle) / Resolution: 2.93 Å 26415 7ua5 EMDB-26415, PDB-7ua5: Structure of dephosphorylated human RyR2 in the closed state Method: EM (single particle) / Resolution: 2.83 Å 26416 7ua9 EMDB-26416, PDB-7ua9: Structure of dephosphorylated human RyR2 in the open state Method: EM (single particle) / Resolution: 3.59 Å
Chemicals	ChemComp-ZN: Unknown entry ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM / Adenosine triphosphate ChemComp-CA: Unknown entry ChemComp-XAN: XANTHINE / Xanthine ChemComp-KVR*: 4-[(7-methoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)methyl]benzoic acid
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / calcium channel / Ryanodine receptor 2