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 diseases. We determined the molecular architecture of native skeletal and cardiac sarcomeres and structures of sarcomeric proteins using cryo-focused-ion-beam milling (cryo-FIB) and electron cryo-tomography (cryo-ET). Our three-dimensional reconstruction of the sarcomere reveals molecular details in the A-band, I-band and Z-disc and demonstrates the organisation of the thin and thick filaments and their cross-links [1,2]. Our reconstruction of the thick filament reveals the three-dimensional organization of myosin heads and tails, myosin-binding protein C (MyBP-C) and titin, elucidating the structural basis for their interaction during muscle contraction [2]. Using sub-tomogram averaging, we determined an in situ structure of a nebulous thin-filament-binding protein, nebulin, at 4.5 Å and demonstrated the molecular mechanism underlying its role as a "molecular ruler", in stabilising thin filament and in regulating myosin binding [3]. We also characterised the structure of a unique double-head myosin conformation, highlighting the inherent structural variability of myosin in muscle [1].

References:
[1] Wang, Z, Grange M et al. (2021), Cell. 184,2135-2150.613
[2] Tamborrini, D et al. (2023), bioRxiv, https://doi.org/10.1101/2023.04.11.536387
[3] Wang, Z, Grange M et al. (2022), Science. 375, eabn1934 doi: 10.1126/science.abn1934Link opens in a new window

Biography: Professor Stefan Raunser is a structural biologist whose research focuses on understanding molecular mechanisms underlying cellular processes in the healthy and diseased organism. He is Director of the Department of Structural Biochemistry at the Max Planck institute of Molecular Physiology, Adjunct Professor at Technical University Dortmund and Honorary Professor at University of Duisburg-Essen. With his research group, he uses a multi-disciplinary approach, including biochemical reconstitutions, high-resolution electron cryomicroscopy (cryo-EM) and electron cryotomography (cryo-ET) primarily to investigate the structure of macromolecular complexes that play a crucial role in cell physiology, with a particular emphasis on toxin-mediated membrane permeation, the molecular details of muscle contraction and the dynamics of the eukaryotic cytoskeleton. A detailed understanding of these processes is of great importance as they ultimately serve to develop pharmaceutical measures to combat disease.

He has authored over 100 papers in the fields of structural and molecular biology and has given over 200 lectures and seminars around the world. He is a scientific member of the Max Planck Society and an elected member of the North Rhine Westphalian Academy of Sciences and Arts, the German National Academy of Sciences Leopoldina and EMBO.