6X36
Pig R615C RyR1 in complex with CaM, EGTA (class 3, closed)
This is a non-PDB format compatible entry.
Summary for 6X36
| Entry DOI | 10.2210/pdb6x36/pdb |
| EMDB information | 22015 22016 22017 22018 22019 |
| Descriptor | Peptidyl-prolyl cis-trans isomerase FKBP1B, Ryanodine Receptor, Calmodulin-1 (3 entities in total) |
| Functional Keywords | receptor, calcium, channel, complex, transport protein-isomerase-calcium binding protein complex, transport protein/isomerase/calcium binding protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 12 |
| Total formula weight | 1684350.83 |
| Authors | Woll, K.W.,Haji-Ghassemi, O.,Van Petegem, F. (deposition date: 2020-05-21, release date: 2021-01-13, 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 Cited by 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: 33547325DOI: 10.1038/s41467-021-21141-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.7 Å) |
Structure validation
Download full validation report
