8Q6T
Helical reconstruction of the relaxed thick filament from FIB milled left ventricular mouse myofibrils
This is a non-PDB format compatible entry.
Summary for 8Q6T
| Entry DOI | 10.2210/pdb8q6t/pdb |
| EMDB information | 18198 |
| Descriptor | Myosin-7, Myosin light chain 3, Myosin regulatory light chain 2, ventricular/cardiac muscle isoform, ... (5 entities in total) |
| Functional Keywords | mammalian, muscle, thick filament, cardiac, motor protein |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 22 |
| Total formula weight | 1879464.47 |
| Authors | Tamborrini, D.,Raunser, S. (deposition date: 2023-08-14, release date: 2023-11-01, Last modification date: 2024-10-23) |
| Primary citation | Tamborrini, D.,Wang, Z.,Wagner, T.,Tacke, S.,Stabrin, M.,Grange, M.,Kho, A.L.,Rees, M.,Bennett, P.,Gautel, M.,Raunser, S. Structure of the native myosin filament in the relaxed cardiac sarcomere. Nature, 623:863-871, 2023 Cited by PubMed Abstract: The thick filament is a key component of sarcomeres, the basic units of striated muscle. Alterations in thick filament proteins are associated with familial hypertrophic cardiomyopathy and other heart and muscle diseases. Despite the central importance of the thick filament, its molecular organization remains unclear. Here we present the molecular architecture of native cardiac sarcomeres in the relaxed state, determined by cryo-electron tomography. Our reconstruction of the thick filament reveals the three-dimensional organization of myosin, titin and myosin-binding protein C (MyBP-C). The arrangement of myosin molecules is dependent on their position along the filament, suggesting specialized capacities in terms of strain susceptibility and force generation. Three pairs of titin-α and titin-β chains run axially along the filament, intertwining with myosin tails and probably orchestrating the length-dependent activation of the sarcomere. Notably, whereas the three titin-α chains run along the entire length of the thick filament, titin-β chains do not. The structure also demonstrates that MyBP-C bridges thin and thick filaments, with its carboxy-terminal region binding to the myosin tails and directly stabilizing the OFF state of the myosin heads in an unforeseen manner. These results provide a foundation for future research investigating muscle disorders involving sarcomeric components. PubMed: 37914933DOI: 10.1038/s41586-023-06690-5 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (18 Å) |
Structure validation
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