7VMN
Structure of recombinant RyR2 (EGTA dataset, class 2, closed state)
This is a non-PDB format compatible entry.
Summary for 7VMN
| Entry DOI | 10.2210/pdb7vmn/pdb |
| EMDB information | 33937 |
| Descriptor | Ryanodine receptor 2, Peptidyl-prolyl cis-trans isomerase FKBP1B, ZINC ION (3 entities in total) |
| Functional Keywords | calcium, calcium channel, calcium transport, ion transport, ionic channel, metal transport, er/sr membrane, ryanodine receptor, ryanodine, receptor, wild type, membrane protein |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 8 |
| Total formula weight | 2210813.15 |
| Authors | Kobayashi, T.,Tsutsumi, A.,Kurebayashi, N.,Kodama, M.,Kikkawa, M.,Murayama, T.,Ogawa, H. (deposition date: 2021-10-09, release date: 2022-08-10, Last modification date: 2024-06-19) |
| Primary citation | Kobayashi, T.,Tsutsumi, A.,Kurebayashi, N.,Saito, K.,Kodama, M.,Sakurai, T.,Kikkawa, M.,Murayama, T.,Ogawa, H. Molecular basis for gating of cardiac ryanodine receptor explains the mechanisms for gain- and loss-of function mutations. Nat Commun, 13:2821-2821, 2022 Cited by PubMed Abstract: Cardiac ryanodine receptor (RyR2) is a large Ca release channel in the sarcoplasmic reticulum and indispensable for excitation-contraction coupling in the heart. RyR2 is activated by Ca and RyR2 mutations are implicated in severe arrhythmogenic diseases. Yet, the structural basis underlying channel opening and how mutations affect the channel remains unknown. Here, we address the gating mechanism of RyR2 by combining high-resolution structures determined by cryo-electron microscopy with quantitative functional analysis of channels carrying various mutations in specific residues. We demonstrated two fundamental mechanisms for channel gating: interactions close to the channel pore stabilize the channel to prevent hyperactivity and a series of interactions in the surrounding regions is necessary for channel opening upon Ca binding. Mutations at the residues involved in the former and the latter mechanisms cause gain-of-function and loss-of-function, respectively. Our results reveal gating mechanisms of the RyR2 channel and alterations by pathogenic mutations at the atomic level. PubMed: 35595836DOI: 10.1038/s41467-022-30429-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
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