Milestone in physiology - The sliding filament model: 1972-2004

The sliding filament model, proposed to explain muscle contraction in 1954, has proven to be very robust. Muscle contraction as well as much of the motility of nonmuscle cells has now been shown to be produced by the relative motion of actin filaments and myosin filaments or myosins attached to cargoes. In addition the mechanism of the microtubule motors kinesin and dynein, a system unknown in 1954, has been shown to work in the same fashion. Although there is considerable homology in the sequences of the catalytic domains of the myosins and kinesins, they appear to have evolved diverse mechanisms for translating changes in the catalytic domain into motion. Most myosins appear to operate by a lever arm motion of the light-chain domain. However, myosin VI takes a long step with a short lever arm, suggesting a mechanism where some region of the protein melts, possibly the coiled-coil rod (Rock et al. 2001). This protein may thus have a mechanism with similarities to that proposed for conventional kinesin. Kinesin appears to operate by alternate docking of its neck linker; however, ncd may operate by a lever arm motion. The only area of motility that has not followed the sliding filament model is the force produced by actin polymerization. The molecular mechanisms of the motor proteins that produce motility are now reasonably well understood, although gaps in our knowledge remain, particularly in the structures of the motor-polymer complexes. These mechanisms were elucidated by innovations and technologies that largely were unimaginable in 1954. We should expect a similar rate of progress in the next 50 yr.