7u9r

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Structure of PKA phosphorylated human RyR2 in the open state

Structural highlights

7u9r is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:ATP, CA, XAN, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[FKB1B_HUMAN] Has the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

Publication Abstract from PubMed

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(2+) 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 A, and reaching local resolutions of 2.25 A, 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(2+) 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.

Structural analyses of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment.,Miotto MC, Weninger G, Dridi H, Yuan Q, Liu Y, Wronska A, Melville Z, Sittenfeld L, Reiken S, Marks AR Sci Adv. 2022 Jul 22;8(29):eabo1272. doi: 10.1126/sciadv.abo1272. Epub 2022 Jul, 20. PMID:35857850[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
2 reviews cite this structure
Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart.
Dridi et al. (2023)
1 more
17 other articles
No citations found

References

  1. ↑ Miotto MC, Weninger G, Dridi H, Yuan Q, Liu Y, Wronska A, Melville Z, Sittenfeld L, Reiken S, Marks AR. Structural analyses of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment. Sci Adv. 2022 Jul 22;8(29):eabo1272. doi: 10.1126/sciadv.abo1272. Epub 2022 Jul, 20. PMID:35857850 doi:http://dx.doi.org/10.1126/sciadv.abo1272

Contents


PDB ID 7u9r

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OCA

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