Molecular characteristics of contractile muscle fibers
One property of the myosin head that is essential for muscle contraction is that it functions as an enzyme adenosine triphosphatase (ATPase).
Myosin filaments are composed of double myosin molecules
Each molecule of myosin, shown in figure A, has a molecular weight of about 480,000. Figure B shows the organization of the many molecules that form a myosin filament, as well as the interaction of this filament on the one hand with the terminals of the two actin filaments.
Figure. A the myosin molecule. B, the combination of many myosin molecules forms a myosin filament. Also shown are thousands of myosin cross-bridges and interactions between the ends of the cross-bridges with adjacent actin filaments.
The myosin molecule (see figure A) consists of six polypeptide chains - two heavy chains, each with a molecular weight of about 200,000, and four light chains with a molecular weight of about 20,000 each. The two heavy chains twist around each other to form a double helix, called the tail of the myosin molecule. One end of each chain is folded bilaterally into a spherical polypeptide structure called a myosin head.
Thus, there are two free ends at one end of the double helix of the myosin molecule. Four light chains are also part of the myosin head, two at each end. These light chains help control the function of the head during muscle contraction.
Myosin filaments are made up of 200 or more individual myosin molecules. The central part of one of these filaments is shown in figure B, where the tails of the myosin molecules bunch together to form the body of the filament, while the many ends of the molecules hang outside. to the sides of the body. In addition, part of the body of each myosin molecule hangs to the side along with the head, thereby providing a branch that sends to the outer end from the stem, as shown in the figure. The branches that protrude and the ends together are called cross bridges. Each cross-bridge is flexible at two points called junctions—one where the branch leaves the body of the myosin filament, and the other where the tip attaches to the branch. Articulated branches allow the ends to either extend outward from the body of the myosin filament or bring them closer to the stem.
The total length of each myosin strand is constant - almost exactly 1.6 m. Note, however, that there is no bridging the ends at the centre of the myosin filament for a distance of about 0.2 µm because the articulated branches extend away from the centre.
Now, to complete the picture, the myosin filament twists so that each successive pair of cross-bridges has an axis displaced from the previous pair by 120 degrees. This twist ensures that the horizontal bridges extend in all directions around the fibre.
Adenosine Triphosphatase activity of the myosin head
Another property of the myosin head that is essential for muscle contraction is that it functions as an enzyme adenosine triphosphatase (ATPase). As explained later, this property allows the head to release ATP and use the energy derived from the high-energy phosphate binding of ATP to fuel contraction.
Actin filaments include actin, tropomyosin, and troponin
The backbone of the actin filament is a double-stranded F-actin protein molecule, depicted by the two lighter coloured filaments in the figure. The two strands are wrapped in a helix in a manner similar to the myosin molecule.
Figure. Actin filaments, consisting of two helices of F-actin molecules and two filaments of tropomyosin molecules, fit into the grooves between actin filaments. Attached to one end of each tropomyosin molecule is a troponin complex that initiates contraction.
Each strand of the F-actin double helix consists of polymerized G-actin molecules, each with a molecular weight of about 42,000. Attached to each one of the G-actin molecules is an ADP molecule. These ADP molecules are believed to be active sites on actin filaments with which cross bridges of myosin filaments interact to induce muscle contraction. The active sites on the two F-actin filaments of the double helix alternate, giving an activity point on the entire actin filament of about 2.7 nm each.
Each actin filament is about 1 µm long. The base of the actin filaments is strongly inserted into the Z-discs; the ends of the filaments protrude in both dimensions located in the space between the myosin molecules, as shown in the figure.
The actin filament also contains another protein, tropomyosin. Each molecule of tropomyosin has a molecular weight of 70,000 and a length of 40 nm.
These molecules are twisted around the sides of the F-actin helix. At rest, the tropomyosin molecules are located on top of the active sites of the actin filaments so that attraction between actin and myosin filaments cannot cause contraction.
Troponin and its role in muscle contraction
Attached discontinuously along the sides of the tropomyosin molecules are additional protein molecules called troponins. These protein molecules are essentially complexing of three loosely bound protein subunits, each of which plays a specific role in controlling muscle contraction.
One of the subunits (troponin I) has a strong affinity for actin, the other (troponin T) for tropomyosin, and the third (troponin C) for calcium ions. This complex is thought to bind tropomyosin to actin. Troponin's strong affinity for calcium ions is thought to initiate contractility, as explained in the next section.
Interaction of one myosin filament, two actin filaments, and calcium ions to induce contraction.
Inhibition of actin filaments by the Troponin–Tropomyosin. complex
Filamentous actin completely devoid of the troponin-tropomyosin complex (but in the presence of magnesium ions and ATP) binds immediately and strongly to the ends of myosin molecules. Then, if the troponin-tropomyosin complex is added to the actin filaments, binding between myosin and actin does not take place. Therefore, it is believed that the active sites on the normal actin filaments of the relaxant muscle are either inhibited or overlaid by the troponin tropomyosin complex. Therefore, the points cannot attach to the ends of the myosin filaments to induce contraction. Before contraction can occur, the inhibitory effect of the troponin-tropomyosin complex itself must be inhibited.
Activation of actin filaments by calcium ions
In the presence of large amounts of calcium ions, the inhibitory effect of troponin-tropomyosin on the actin filament itself is again inhibited. The mechanism of this inhibition is unknown, but one hypothesis is as follows: When calcium ions combine with troponin C, each of which can bind strongly to up to four calcium ions, the troponin complex is thought to undergo a conformational change that in some way pulls on the tropomyosin molecule and moves deeper into the grooves between the two actin filaments. This activity "unmasks" the active sites of actin, thereby allowing these active sites to attract the ends of the myosin cross-bridge and cause contraction to proceed. Although this mechanism is hypothetical, it highlights that the normal relationship between the troponin tropomyosin complex and actin is altered by calcium ions, giving rise to a new condition that leads to contractility.
Interaction of "activated" actin filaments and Myosin cross-bridges - The "vertical walk" theory of contraction
As soon as the actin filaments are activated by calcium ions, the ends of the cross-bridges from the myosin filaments become attracted to the active sites of the actin filaments, and this, in some way, induces contraction. happening. Although the exact way in which the interaction between cross-bridges and actin induces contraction is still somewhat theoretical, one hypothesis for which substantial evidence exists is the "vertical walk" theory. or “latch”) of contraction.
Figure. Mechanism of "vertical walking" for muscle contraction
The figure demonstrates the hypothesis of longitudinal walking with contraction. The figure shows the ends of two cross-bridges attaching to and detaching from the active sites of an actin filament.
When one end attaches to an active site, this binding simultaneously causes profound changes in the intramolecular energy between the head and its cross-bridge.
The new adjustment of energy causes the head to tilt toward the branch and pull the actin filament with it. This tilt of the head is called a power stroke. Immediately after tilting, the head then automatically detaches from the operating position. Next, the head returns to its extension direction. In this position, it combines with a new active site further down along the actin filament; The head then tilts again to cause a new work, and the actin filament moves one step further. Thus, the ends of the cross-bridges bend back and forth and step by step walk along the actin filament, pulling the ends of two consecutive actin filaments toward the centre of the myosin filament.
Each one of the cross-bridges is said to operate independently of all the others, each attaching and pulling in a continuously repeated cycle. So, the greater the number of cross-bridges in contact with the actin filament at any given time, the greater the force of contraction.
ATP as an energy source for contraction - Chemical events in the movement of Myosin heads
When a muscle contracts, work is done, and energy is needed. A large amount of ATP is broken down to form ADP during contraction, and the more work done by the muscle, the more ATP is extracted; This phenomenon is known as the Fenn effect. The following sequence of events is believed to be the method by which this effect occurs:
1. Before contraction begins, the ends of the cross-bridges attach to ATP. The active ATPase of the myosin head immediately cleaves ATP but leaves the cleavage product, ADP plus phosphate ion, bound to the tip.
In this state, the shape of the head is so that it extends perpendicular to the actin filament but has not yet attached to the actin.
2. When the troponin-tropomyosin complex binds to calcium ions, the active sites on the actin filament are revealed and the myosin heads then bind to these sites, as shown in the figure.
3. The association between the tip of the cross-bridge and the active site of the actin filament causes a conformational change at the tip, causing the tip to tilt towards the branch of the cross-bridge and perform work for the pull. actin filaments. The energy that activates the work is the energy that has been stored, like a spring "tipping," by the conformational change that occurred in the head when the ATP molecule was previously split.
4. Once the tip of the cross-bridge is tilted, the release of ADP and phosphate ion that was previously attached to the tip is allowed. At the site of the release of ADP, a new molecule of ATP binds. This binding of new ATP causes dissociation of the head from actin.
5. After the head has separated from the actin, the new molecule of ATP is separated to start the next cycle, resulting in new work done. That is, the energy "boils up" again so that the head returns to its perpendicular state, ready to begin a new cycle of work.
6. When the tip (with its stored energy derived from the dissociated ATP) binds to a new active site on the actin filament, it becomes unspooled and once again performs a new job.
Thus, the process is repeated over and over until the actin filaments pull the Z membrane close to the ends of the myosin filaments or until the load on the muscle becomes too great for more traction to occur out.