7QIN

In situ structure of actomyosin complex in skeletal sarcomere

Summary for 7QIN

• Entry DOI: 10.2210/pdb7qin/pdb
• Related: 7QIM 7QIO
• EMDB information: 13990 13991 13992 13993 13998
• Descriptor: Actin, alpha skeletal muscle, nebulin (mouse), tropomyosin, alpha-1 (mouse), ... (9 entities in total)
• Functional Keywords: skeletal muscle, sarcomere, thin filament, cross-bridge, contractile protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 13
• Total formula weight: 452374.78

Authors

Wang, Z.,Grange, M.,Pospich, S.,Wagner, T.,Kho, A.L.,Gautel, M.,Raunser, S. (deposition date: 2021-12-15, release date: 2022-02-16, Last modification date: 2022-03-02)

Primary citation

Wang, Z.,Grange, M.,Pospich, S.,Wagner, T.,Kho, A.L.,Gautel, M.,Raunser, S.
Structures from intact myofibrils reveal mechanism of thin filament regulation through nebulin.
Science, 375:eabn1934-eabn1934, 2022

PubMed Abstract: In skeletal muscle, nebulin stabilizes and regulates the length of thin filaments, but the underlying mechanism remains nebulous. In this work, we used cryo-electron tomography and subtomogram averaging to reveal structures of native nebulin bound to thin filaments within intact sarcomeres. This in situ reconstruction provided high-resolution details of the interaction between nebulin and actin, demonstrating the stabilizing role of nebulin. Myosin bound to the thin filaments exhibited different conformations of the neck domain, highlighting its inherent structural variability in muscle. Unexpectedly, nebulin did not interact with myosin or tropomyosin, but it did interact with a troponin T linker through two potential binding motifs on nebulin, explaining its regulatory role. Our structures support the role of nebulin as a thin filament "molecular ruler" and provide a molecular basis for studying nemaline myopathies.

PubMed: 35175800
DOI: 10.1126/science.abn1934

Experimental method

ELECTRON MICROSCOPY (6.6 Å)