The molecular basis of cross-bridge function.

Our understanding of the physiology of muscle depends critically on the resolution of the available anatomy. Early insight was provided by light microscopy. However, the first radical new insight was provided by electron microscopy. Ultimately, an understanding in physicochemical terms is only possible if the structures of the components in various physiological states are known at atomic resolution. Some of these have become known in the last 15 years and now allow us to describe how the hydrolysis of ATP by the component proteins actin and myosin leads to movement. HE Huxley was able to show that the filaments in the sarcomere were organised on a hexagonal lattice '" ^. The seminal works of HE Huxley and Jean Hanson ' and AF Huxley and Niedergerke'' showed that the two sets of filaments in the sarcomere glide over each other without altering their length. Through the work of HE Huxley, Jean Hanson and W. Hasselbach it was discovered that the thick filaments contain myosin and the thin filaments contain actin. The myosin molecule consists of two heavy chains and four light chains. A soluble proteolytic fragment of myosin, heavy mero-myosin that contains the 2 globular "heads" of myosin carries the ATP-ase activity ^ the rest of the molecule forming a long double a-helical coiled-coil involved in filament formation. The ATP-ase activity was later shown to reside in the "head" fragment (sub-fragment-1 or SI)*"* that constitutes the cross-bridge (see below).