8Q4G

Thin filament from FIB milled relaxed left ventricular mouse myofibrils

Summary for 8Q4G

• Entry DOI: 10.2210/pdb8q4g/pdb
• EMDB information: 18147
• Descriptor: Actin, alpha cardiac muscle 1, Tropomyosin alpha-1 chain (2 entities in total)
• Functional Keywords: muscle sarcomere calcium-free cardiac thin-filament, structural protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 9
• Total formula weight: 331979.36

Authors

Tamborrini, D.,Wang, Z.,Wagner, T.,Tacke, S.,Stabrin, M.,Grange, M.,Kho, A.L.,Bennet, P.,Rees, M.,Gautel, M.,Raunser, S. (deposition date: 2023-08-06, 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

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: 37914933
DOI: 10.1038/s41586-023-06690-5

Experimental method

ELECTRON MICROSCOPY (8 Å)