The molecular basis of activation

As mentioned earlier, pure actin will react with pure myosin so as to split ATP in the absence of calcium ions. But if tropomyosin and troponin are also present, the actin—myosin interaction and ATP splitting will occur in the presence of calcium ions. Hence it is probable that tropomyosin and troponin are intimately involved in the control of muscular contraction.

Tropomyosin is a fibrous protein which will bind to actin and troponin. Troponin is a globular protein with three subunits: one binds to actin, another to tropomyosin and a third combines reversibly with calcium ions, undergoing a conformational change in the process.

The molecular ratios of actin, tropomyosin and troponin in the muscle are 7:1:1. A model of the thin filament incorporating these ratios is shown in Fig. 10.15c, where the tropomyosin molecules lie in the grooves between the two chains of actin monomers and a troponin molecule is attached with each tropomyosin molecule to every seventh actin monomer. This arrangement would give a repeat distance of (7 X 5.5) = 38.5 nm for the troponin and tropomyosin, which agrees well with the observation of X-ray reflections at this distance.

Fig. 10.18. One of the models proposed to show how movement of tropomyosin molecules may affect actin-myosin interactions. A thin filament is seen in cross-section with actin (A) and tropomyosin (TM) molecules. Two myosin S1 subunits are shown attached to the thin filaments. Tropomyosin positions are shown for the muscle at rest (dotted circle) and when active (contours). Other models give somewhat different shapes and positions for the various protein molecules, but all agree that the tropomyosin molecule moves into the 'groove' between the actin monomers on activation. It is thought that the S1 heads are unable to attach to the actin filament until this movement takes place. From Huxley (1976).

Fig. 10.18. One of the models proposed to show how movement of tropomyosin molecules may affect actin-myosin interactions. A thin filament is seen in cross-section with actin (A) and tropomyosin (TM) molecules. Two myosin S1 subunits are shown attached to the thin filaments. Tropomyosin positions are shown for the muscle at rest (dotted circle) and when active (contours). Other models give somewhat different shapes and positions for the various protein molecules, but all agree that the tropomyosin molecule moves into the 'groove' between the actin monomers on activation. It is thought that the S1 heads are unable to attach to the actin filament until this movement takes place. From Huxley (1976).

Evidence about the structure of the thin filament under different conditions has been obtained from X-ray diffraction measurements and from computer analysis simulating optical diffraction of electron micrographs. It seems likely that the binding of calcium by a troponin molecule causes a change in its shape which draws the tropomyosin molecule to which it is attached further into the groove between the two chains of actin monomers (Fig. 10.18). In the resting condition it looks as though the tropomyosin molecules prevent actin—myosin interaction by covering the myosin binding sites on the actin monomers. So this movement on activation has the exciting consequence that each tropomyosin molecule uncovers the myosin-binding sites on seven actin monomers. The myosin heads can then combine with the actin and so the muscle contracts. It is a very elegant piece of biological machinery.

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A Disquistion On The Evils Of Using Tobacco

A Disquistion On The Evils Of Using Tobacco

Among the evils which a vitiated appetite has fastened upon mankind, those that arise from the use of Tobacco hold a prominent place, and call loudly for reform. We pity the poor Chinese, who stupifies body and mind with opium, and the wretched Hindoo, who is under a similar slavery to his favorite plant, the Betel but we present the humiliating spectacle of an enlightened and christian nation, wasting annually more than twenty-five millions of dollars, and destroying the health and the lives of thousands, by a practice not at all less degrading than that of the Chinese or Hindoo.

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