EMD-13992

Subtomogram averaging
8.9 Å
EMD-13992 Deposition: 15/12/2021
Map released: 02/03/2022
Last modified: 02/03/2022
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-13992

In situ structure of myosin neck domain in skeletal sarcomere (centered on essential light chain)

EMD-13992

Subtomogram averaging
8.9 Å
EMD-13992 Deposition: 15/12/2021
Map released: 02/03/2022
Last modified: 02/03/2022
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Mus musculus
Sample: Mouse psoas muscle myofibrils

Deposition Authors: Wang Z , Grange M , Pospich S , Wagner T , Kho AL , Gautel M , Raunser S
Structures from intact myofibrils reveal mechanism of thin filament regulation through nebulin.
Wang Z , Grange M , Pospich S , Wagner T , Kho AL , Gautel M , Raunser S
(2022) Science , 375 , eabn1934 - eabn1934
PUBMED: 35175800
DOI: doi:10.1126/science.abn1934
ISSN: 1095-9203
ASTM: SCIEAS
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.