Actin-myosin cross-bridges

Until recently, there was little doubt that metabolic acidosis could decrease muscle contractility. Purported mechanisms included inhibition of glycolytic rate, reduced Ca release from the sarcoplasmic reticulum, and reduction of actin-myosin cross-bridge activation by H" " competitive inhibition of Ca " " binding to troponin-C (90). Despite the biological plausibility though, investigators have reported no effect or marginal effect... 

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.

ATP binds to the myosin cross-bridges, leading to release of the bond between actin and myosin. 

Figure 13.7 A diagram of the actin helix showing position of the tropomyosin. Both actin chains are flanked by tropomyosin molecules, which are long string-like molecules that span seven actin monomers. The troponin complex is attached to the tropomyosin but is not shown. From this diagram, it should be clear how the tropomyosin molecule can conceal the actin-binding sites for the myosin cross-bridges in the relaxed condition. A small conformational change in tropomyosin exposes the sites for attachment of the cross-bridges.

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

Figure 13.16 A summary of the control of muscle contraction by the motor neurone. When an electrical impulse arrives at the junction between a nerve axon and a muscle fibre, a small amount of acetylcholine is released. This initiates an action potential which is transmitted throughout the fibre via the T-tubules. This causes the sarcoplasmic reticulum to release Ca ions which initiate contraction of the myofibrils via changes in troponin and tropomyosin. Thus sites on the actin for binding of the myosin cross-bridges are exposed.

Harford, J. J., and Squire, J. M. (1992). Evidence for structurally different attached states of myosin cross-bridges on actin during contraction of fish muscle. Biophys. /. 63, 387-396. 

However, a nerve impulse to the muscle triggers a release of Ca2+ from the sarcoplasmic tubular system, where it is ordinarily bound, which increases the intracellular Ca2+ concentration to 10 5-10 6M. This level of Ca2+ allows the actin in the thin filament to accept the energized-ADP-myosin cross-bridge to initiate contraction. As each cross-bridge completes the swivel part of its cycle, it loses the bound ADP and immediately accepts a molecule of ATP that is always supplied to living muscle. The ATP immediately causes a dissociation of the actin-myosin complex, and the myosin catalyzes the hydrolysis of ATP to yield the myosin—ADP energized state again, ready to repeat the cycle. 

Warshaw DM, Desrosiers JM, Work SS, Trybus KM (1990) Smooth muscle myosin cross-bridge interactions modulate actin filament shding velocity in vitro. J Cell Biol 111 453463... 

Figure 8.56. Stereo view in space-filling representation of a scallop cross-bridge (SI) view of the actin binding site on myosin cross-bridge, with continuity of the cleft from the ADP-BeF, binding site to the actin binding site that dissociates on ATP binding (A) Near-rigor state without nucleotide in the binding...

Calcium Ion Binding Displaces Tropomyosin to Open the Tight Binding Site on Actin for Hydrophobic Association with the Myosin Cross-bridge... 

Figure E.5. Stereo view (cross-eye) in space-filling representation of the scallop muscle cross-bridge(Sl) viewed approximately from the side of the actin binding site on myosin cross-bridge for the purpose of locating the narrow clefts that direct the apolar-polar repulsive force. (A) The hydrophobic association of the near-rigor state. (Prepared using...

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 14.17 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.

---