6W1N

Pig Ryanodine Receptor (WT) in 5mM EGTA condition

This is a non-PDB format compatible entry.

Summary for 6W1N

• Entry DOI: 10.2210/pdb6w1n/pdb
• EMDB information: 21513
• Descriptor: Peptidyl-prolyl cis-trans isomerase FKBP1B, Ryanodine Receptor, ZINC ION (3 entities in total)
• Functional Keywords: receptor, calcium, channel, complex, transport protein-isomerase complex, transport protein/isomerase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 2091165.51

Authors

Woll, K.W.,Haji-Ghassemi, O.,Van Petegem, F. (deposition date: 2020-03-04, release date: 2021-01-06, Last modification date: 2024-03-06)

Primary citation

Woll, K.A.,Haji-Ghassemi, O.,Van Petegem, F.
Pathological conformations of disease mutant Ryanodine Receptors revealed by cryo-EM.
Nat Commun, 12:807-807, 2021

PubMed Abstract: Ryanodine Receptors (RyRs) are massive channels that release Ca from the endoplasmic and sarcoplasmic reticulum. Hundreds of mutations are linked to malignant hyperthermia (MH), myopathies, and arrhythmias. Here, we explore the first MH mutation identified in humans by providing cryo-EM snapshots of the pig homolog, R615C, showing that it affects an interface between three solenoid regions. We also show the impact of apo-calmodulin (apoCaM) and how it can induce opening by bending of the bridging solenoid, mediated by its N-terminal lobe. For R615C RyR1, apoCaM binding abolishes a pathological 'intermediate' conformation, distributing the population to a mixture of open and closed channels, both different from the structure without apoCaM. Comparisons show that the mutation primarily affects the closed state, inducing partial movements linked to channel activation. This shows that disease mutations can cause distinct pathological conformations of the RyR and facilitate channel opening by disrupting interactions between different solenoid regions.

PubMed: 33547325
DOI: 10.1038/s41467-021-21141-3

Experimental method

ELECTRON MICROSCOPY (4 Å)