Electron cryo-tomography of native vertebrate skeletal sarcomeres revealed the 3D organization of actin and myosin, including two conformations of double-head myosin at ~10 Å resolution.
Provides high-resolution structural insights into the fundamental organization of vertebrate skeletal muscle sarcomeres, serving as a foundation for understanding muscle diseases.
Sarcomeres are force-generating and load-bearing devices of muscles. A precise molecular picture of how sarcomeres are built underpins understanding their role in health and disease. Here, we determine the molecular architecture of native vertebrate skeletal sarcomeres by electron cryo-tomography. Our reconstruction reveals molecular details of the three-dimensional organization and interaction of actin and myosin in the A-band, I-band, and Z-disc and demonstrates that α-actinin cross-links antiparallel actin filaments by forming doublets with 6-nm spacing. Structures of myosin, tropomyosin, and actin at ~10 Å further reveal two conformations of the "double-head" myosin, where the flexible orientation of the lever arm and light chains enable myosin not only to interact with the same actin filament, but also to split between two actin filaments. Our results provide unexpected insights into the fundamental organization of vertebrate skeletal muscle and serve as a strong foundation for future investigations of muscle diseases.
Wang et al. (2021) studied vertebrate skeletal muscle structure. Electron cryo-tomography of native vertebrate skeletal sarcomeres revealed the 3D organization of actin and myosin, including two conformations of double-head myosin at ~10 Å resolution.