The molecular basis for sarcomere organization in vertebrate skeletal muscle

Zhexin Wang, Michael Grange, Thorsten Wagner, Ay Lin Kho, Mathias Gautel, Stefan Raunser*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2135-2150.e13
JournalCell
Volume184
Issue number8
DOIs
Publication statusPublished - 15 Apr 2021

Keywords

  • actin
  • electron tomography
  • muscle
  • myosin
  • sarcomere
  • structure
  • tropomyosin
  • Z-disc

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