M uscle contraction is produced by the intermittent and asynchronous "working strokes" of many individual myosin molecules that "row" the "thin" actin filaments past the "thick" myosin filaments. Actomyosin cross bridges are formed by the "heads" of the myosin II molecules that protrude from the shaft of the myosin thick filament and interact with actin filaments in a cyclic manner, hydrolyzing a single ATP molecule in each cycle. Muscle myosin II molecules are nonprocessive molecular motors, i.e., ones that are released from actin after each catalytic cycle. In contrast, some nonmuscle (or "unconventional") myosins are processive motors that undergo multiple catalytic cycles and mechanical steps for each diffusional encounter with actin. The myosin superfamily consists of at least 18 different classes distributed across plant and animal kingdoms and with great diversity of cellular functions (17). Reflecting these functional differences, there is considerable sequence and structural diversity in the tail part of the molecule, whereas the motor domain or head of the molecule is well conserved. It is assumed that throughout the myosin family the basic mechanism of movement and force production is the same and occurs, as already mentioned, by the cyclical interaction of the myosin motor domain with Factin coupled to the breakdown of ATP.Of all of the different members of the myosin family, muscle myosin II is surely the best studied. It provides a paradigm for studying the structure/function relationships and how conformational changes might generate movement and force. Here we will focus mainly on our current understanding of this myosin that has been optimized for a variety of contractile functions, from the rapid repetitive contraction cycles of insect flight muscles to the extremely slow contractions of tonic smooth muscle. In addition, we will also touch on some single-molecule studies with unconventional myosin I. The recent discovery of a two-step working stroke of myosin I gives important insight into the mechanism of cross-bridge movement and force production. These experiments (described in Ref. 19) might offer insight into the molecular mechanism that allows force maintenance to be economical from an energetic point of view, in particular in a state of tonic contraction such as "latch" and "catch" of vertebrate and invertebrate smooth muscles. Recently developed single-molecule mechanical techniques have made it possible to address the mechanism of movement and force production during a single cross-bridge cycle in an unequivocal way. Structure of myosin II motorsMuscle myosin II heads [proteolytic subfragment 1 (S1)] consist of 1) an NH 2 -terminal catalytic (or motor) domain containing the actin-binding sites and the ATPase catalytic site and 2) a neck region formed by an extended ,-helix, to which are bound the essential and regulatory light chains (Refs. 7 and 15; cf. Fig. 1). S1 retains all of the motor functions of myosin in vitro, i.e., the ability to produce motility and force. Furthermore, limi...

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