Myosin-actin motors: the partnership goes atomic.

Muscle contraction is one of biology's grandest and most powerful ballets. As choreographed in striated muscle, the ATP-driven interaction of myosin with actin can develop mechanical power of 100-200 watts/kg, allowing one horse to generate up to 12-15 horsepower [1]. The ordered lattices of myofilaments with projecting myosin heads seen by electron microscopy (EM) suggest that muscle might operate like a clockwork toy, its crossbridges making rowing motions powering the sliding of actin filaments [2,3]. Indeed, the latest tours de force of time-resolved X-ray diffraction from muscle show forceproducing crossbridges not only making the necessary attachment to actin [4] but also swinging through a power stroke from an angle of 90 ° to one of about 45 ° during the 2 ms recovery after rapid shortening steps of 50& [5]. But other recent evidence blurs the picture, suggesting that crossbridges hop [6] and jitter like blurred dervishes [7J through disorderly [8,9] steps that seem too long for each head [10] or too many for each ATP hydrolyzed [11]. The simple mechanical model is clearly inadequate, and more intricate models require atomic detail. Prospects for a real understanding of actin-myosin interactions picked up three years ago with the atomic structure of actin from Kabsch and Holmes et al. [12,13], and took off this sum mer with papers detailing the three-dimensional atomic structure of the myosin head from Rayment et al. [14] and the fitting of these X-ray structures into EM reconstructions of native ATP-free (rigor) complexes where actin is saturated with firmly attached myosin heads [ 15,16].