1. ^* Department of Biophysics, Cell and Molecular Biology, King's College London, 26-29 Drury Lane, London WC2B 5RL, UK
2. ^† Dipartimento di Scienze Fisiologiche, Università degli Studi di Firenze, Viale GB Morgagni 63, 1-50134 Firenze, Italy
3. ^‡ National Institute for Medical Research, Mill Hill, London NW7 1AA, UK

Abstract

MOTOR proteins such as myosin, dynein and kinesin use the free energy of ATP hydrolysis to produce force or motion, but despite recent progress^1–4 their molecular mechanism is unknown. The best characterized system is the myosin motor which moves actin filaments in muscle^5–12. When an active muscle fibre is rapidly shortened the force first decreases, then partially recovers over the next few milliseconds⁵. This elementary force-generating process is thought to be due to a structural 'working stroke' in the myosin head domain^5–9, although structural studies have not provided definitive support for this^10–12. X-ray diffraction has shown that shortening steps produce a large decrease in the intensity of the 14.5 nm reflection arising from the axial repeat of the myosin heads along the filaments^13,14. This was interpreted as a structural change at the end of the working stroke, but the techniques then available did not allow temporal resolution of the elementary force-generating process itself. Using improved measurement techniques, we show here that myosin heads move by about 10 nm with the same time course as the elementary force-generating process.