Journal
SCIENCE
Volume 375, Issue 6582, Pages 738-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abn1934
Keywords
-
Categories
Funding
- Max Planck Society
- Wellcome Trust (Collaborative Award in Sciences) [201543/Z/16/Z]
- European Research Council under the European Union's Horizon 2020 Programme (ERC2019-SyG) [856118]
- Medical Research Council [MR/R003106/1]
- EMBO Long-Term Fellowship
- BHF Chair of Molecular Cardiology
- European Research Council (ERC) [856118] Funding Source: European Research Council (ERC)
- Wellcome Trust [201543/Z/16/Z] Funding Source: Wellcome Trust
Ask authors/readers for more resources
This study reveals the structure of nebulin bound to thin filaments and demonstrates its stabilizing role. It also highlights the different interactions of nebulin with actin and myosin, as well as its interaction with a troponin T linker, explaining its regulatory function.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available