Myosin filament cross-bridge

Myosin heads form cross-bridges between the actin and myosin filaments... 

Within each sarcomere the relative sliding of thick and thin filaments is brought about by "cross-bridges," parts of the myosin molecules that stick out from the myosin filaments and interact cyclically with the thin actin filaments, transporting them hy a kind of rowing action. During this process, the hydrolysis of ATP to ADP and phosphate couples the conformational... 

Figure 14.12 The swinging cross-bridge model of muscle contraction driven by ATP hydrolysis, (a) A myosin cross-bridge (green) binds tightly in a 45 conformation to actin (red), (b) The myosin cross-bridge is released from the actin and undergoes a conformational change to a 90 conformation (c), which then rebinds to actin (d). The myosin cross-bridge then reverts back to its 45° conformation (a), causing the actin and myosin filaments to slide past each other. This whole cycle is then repeated.

Figure 14.17 A sequence of events combining the swinging cross-bridge model of actin and myosin filament sliding with structural data of myosin with and without bound nucleotides.

How can hydrolysis of ATP produce macroscopic movement Muscle contraction essentially consists of the cychc attachment and detachment of the S-1 head of myosin to the F-actin filaments. This process can also be referred to as the making and breaking of cross-bridges. The attachment of actin to myosin is followed by conformational changes which are of particular importance in the S-1 head and are dependent upon which nucleotide is present (ADP or ATP). These changes result... 

Z line The junction between neighbouring actin filaments that forms the border between sarcomeres. It has a Z-shaped appearance on the diagram. M line The middle zone of the sarcomere, formed from the junction between neighbouring myosin filaments. There are no cross-bridges in this region. 

Figure 13.5 Electron micrograph of part of a longitudinal section of a myofibril. Identification of components and the mechanism of contraction. When a muscle fibre is stimulated to contract, the actin and myosin filaments react by sliding past each other but with no change in length of either myofilament. The thick myosin strands in the A band are relatively stationary, whereas the thin actin filaments, which are attached to the Z discs, extend further into the A band and may eventually obliterate the H band. Because the thin filaments are attached to Z discs, the discs are drawn toward each other, so that the sarcomeres, the distance between the adjacent Z-discs, are compressed, the myofibril is shortened, and contraction of the muscle occurs. Contraction, therefore, is not due to a shortening of either the actin or the myosin filaments but is due to an increase in the overlap between the filaments. The force is generated by millions of cross-bridges interacting with actin filaments (Fig. 13.6). The electron micrograph was kindly provided by Professor D.S. Smith.

Figure 13.6 Myosin and actin molecules and myosin crossbridges. Each kind of filament is composed of a different protein myosin in the thick filaments and actin in the thin filaments. In the case of actin, the individual F-actins are more or less spherical but a large number of these combine to produce a long chain, two of which wind around each other, rather like a rope, to produce the thin filament. The myosin molecule is more complex and shaped somewhat like a golf club. To form the thick filament, the shafts aggregate to leave the heads protruding on all sides. These heads form the cross-bridges and are responsible for pulling the thin filaments into the spaces between the thick filaments (see Figure 13.5).

One head of the myosin cross-bridge attaches to the actin filament. 

It is troponin that responds to the increased Ca centration. The Ca ions bind to Tn-C, which then binds to Tn-I and causes a conformational change in Tn-T. This results in a conformational change in tropomyosin that exposes sites on the actin filament for binding with the myosin head of the cross-bridge. The process can be summarised as follows (see also Figure 13.16) ... 

At the ultrastructural level, flatworm muscle resembles smooth muscle with individual, non-striated myofibrils being delimited by the sarcolemma and interconnected by gap junctions. Also, flatworm muscles lack a T-tubule system that is characteristic of striated muscle in other animal groups. The contractile portion of flatworm myofibrils contains thick myosin and thin actin filaments that connect with the sarcolemma via attachment plaques or desmo-somes. Actomyosin cross-bridges have been reported and where overlap has been observed, ratios that vary from 9 1 to 12 1 have been observed. Although flatworm muscle is mostly non-striated, pseudo-striated (e.g. in the tail of schistosome cercariae Dorsey et al., 2002 Mair et al., 2003) and obliquely striated (e.g. tentacular bulb of the trypanorhynch, Crillotia eri-naceus Ward et al., 1986) muscles have been reported. It is presumed that the role played by these structures has demanded the development... 

FIGURE 13-3 Possible mechanism of action of dantrolene sodium (DantriurrQ. Dantrolene blocks channels in the sarcoplasmic reticulum, thus interfering with calcium release onto the contractile [actin, myosin] filaments. Muscle contraction is reduced because less calcium is available to initiate cross-bridge formation between actin and myosin filaments. 

Squire, J. M. (1972). General model of myosin filament structure. II. Myosin filaments and cross-bridge interactions invertebrate striated and insect flight muscles./. Mol. Biol. 72, 125-138. 

Actin, the major constituent of the thin filaments, can exist as monomeric globular G-actin or as polymerized fibrous F-actin. The actin filaments are connected to the thick filaments by cross-bridges formed by the SI heads of myosin. 

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