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Elastic bending and active tilting of myosin heads during muscle contraction

Nature volume 396, pages 383–387 (1998)Cite this article

Abstract

Muscle contraction is driven by a change in shape of the myosin head region that links the actin and myosin filaments1,2. Tilting of the light-chain domain of the head with respect to its actin-bound catalytic domain is thought to be coupled to the ATPase cycle3,4,5,6. Here, using X-ray diffraction and mechanical data from isolated muscle fibres, we characterize an elastic bending of the heads that is independent of the presence of ATP. Together, the tilting and bending motions can explain force generation in isometric muscle, when filament sliding is prevented. The elastic strain in the head is 2.0–2.7 nm under these conditions, contributing 40–50% of the compliance of the muscle sarcomere. We present an atomic model for changes in head conformation that accurately reproduces the changes in the X-ray diffraction pattern seen when rapid length changes are applied to muscle fibres both in active contraction and in the absence of ATP. The model predictions are relatively independent of which parts of the head are assumed to bend or tilt, but depend critically on the measured values of filament sliding and elastic strain.

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Figure 1: Changes in force and intensity of the M3 X-ray reflection (IM3) produced by rapid length oscillations.
Figure 2: Changes in force and IM3 produced by length oscillations with 320 µs period in rigor.
Figure 3: Structural model for elastic bending and ATP-driven tilting of the light-chain domain of the myosin head.

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Acknowledgements

We thank the non-crystalline diffraction and detector development teams at the CLRC Daresbury Laboratory for hardware and software for the X-ray measurements, A. Aiazzi and M.Dolfi for skilled mechanical and electronic assistance, and the UK MRC, EC, Intas, CNR (Italy), and Telethon (Italy) for financial support.

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Authors and Affiliations

  1. Randall Institute, King's College London, London, WC2B 5RL, UK

    Ian Dobbie & Malcolm Irving

  2. Dipartimento di Scienze Fisiologiche, Università degli Studi di Firenze, Viale GB Morgagni 63, Firenze, I-50134, Italy

    Marco Linari, Gabriella Piazzesi, Massimo Reconditi & Vincenzo Lombardi

  3. Institute of Mechanics, Moscow State University, Moscow, 119899, Russia

    Natalia Koubassova

  4. National Institute for Medical Research, Mill Hill, NW7 1AA, London, UK

    Michael A. Ferenczi

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  1. Ian Dobbie
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  7. Vincenzo Lombardi
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Dobbie, I., Linari, M., Piazzesi, G. et al. Elastic bending and active tilting of myosin heads during muscle contraction. Nature 396, 383–387 (1998). https://doi.org/10.1038/24647

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