Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rotating crossbridge model for muscle contraction proposes that force is produced by a change in angle of the crossbridge between the overlapping thick and thin filaments. Myosin, the major component of the thick filament, is comprised of two heavy chains and two pairs of light chains. Together they form two globular heads, which give rise to the crossbridge in muscle, and a coiled-coil rod, which forms the shaft of the thick filament. The isolated head fragment, subfragment-1 (S1), contains the ATPase and actin-binding activities of myosin (Fig. 1). Although S1 seems to have the requisite enzymatic activity, direct evidence that S1 is sufficient to drive actin movement has been lacking. It has long been recognized that in vitro movement assays are an important approach for identifying the elements in muscle responsible for force generation. Hynes et al. showed that beads coated with heavy meromyosin (HMM), a soluble proteolytic fragment of myosin consisting of a part of the rod and the two heads, can move on Nitella actin filaments. Using the myosin-coated surface assay of Kron and Spudich, Harada et al. showed that single-headed myosin filaments bound to glass support movement of actin at nearly the same speed as intact myosin filaments. These studies show that the terminal portion of the rod and the two-headed nature of myosin are not required for movement. To restrict the region responsible for movement further, we have modified the myosin-coated surface assay by replacing the glass surface with a nitrocellulose film. Here we report that myosin filaments, soluble myosin, HMM or S1, when bound to a nitrocellulose film, support actin sliding movement (Fig. 2). That S1 is sufficient to cause sliding movement of actin filaments in vitro gives strong support to models of contraction that place the site of active movement in muscle within the myosin head.
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PMID:Myosin subfragment-1 is sufficient to move actin filaments in vitro. 295 22

Whether the two heads of skeletal muscle myosin work independently or cooperatively remains an open question in muscle biophysics. While individual myosin heads are sufficient for ATPase activity (Reisler (1980) J Mol Biol 138: 93-107) and force production (Harada et al. (1987) Nature 326: 805-808), it has also been reported that in situ, the two heads of a myosin molecule work cooperatively (Chaen et al. (1986) J Biol Chem 261(29): 13,632-13,636). To examine the role of cross-bridge cooperativity on isometric contraction and unloaded shortening we progressively inactivated myosin cross-bridges via titration with para-phenylenedimaleimide. The resting fiber ATPase was measured to provide an estimate of the fraction of active cross-bridges remaining during the titration. Isometric force and unloaded shortening velocity decline more rapidly than the resting ATPase as the titration proceeds. This is inconsistent with models for independent force generation and suggests cooperative action of myosin cross-bridges when muscle is isometrically contracting or shortening under zero load. However the degree of cooperativity depends on the type of muscle activity. While isometric force declines in a manner consistent with pair-wise cooperative action of myosin heads, unloaded shortening velocity declines more rapidly (greater cooperativity). Therefore, myosin cross-bridges in situ may be capable of at least two types of cooperative interactions, pair-wise cooperativity (when isometric) and another form of cooperativity that is sensitive to longer range interactions transmitted from other cross-bridges in the ensemble (during unloaded shortening).
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PMID:Cross-bridge cooperativity during isometric contraction and unloaded shortening of skeletal muscle. 1196 67