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Molecular motors and the mechanism of muscle contraction
Objectives
- 1.
List the common principles that apply to all molecular motors: myosin, kinesin, and dynein.
- 2.
Describe the structure of a skeletal muscle cell and the organization of its contractile elements, and compare and contrast this with the structure of cardiac and smooth muscle.
- 3.
Describe the sliding filament mechanism of muscle contraction.
- 4.
Describe the coupling between the mechanical motions of the myosin motor and the steps involved in ATP hydrolysis during cross-bridge cycling.
- 5.
Describe how Ca 2+ interacts with the regulatory proteins troponin and tropomyosin to activate contraction in skeletal and cardiac muscle.
- 6.
Describe how Ca 2+ activates contraction in smooth muscle by promoting the phosphorylation of myosin regulatory light chain.
Molecular motors produce movement by converting chemical energy into kinetic energy
Movement is one of the defining characteristics of all living creatures. Motility is an essential feature of many biological activities, such as the beating of cilia and flagella, cell movement, cell division, development and maintenance of cell architecture, and muscle contraction, the main topic of this and the next two chapters. Indeed, the normal function of all cells requires the directional transport, within the cell, of numerous substances and organelles, such as vesicles, mitochondria, chromosomes, and macromolecules (e.g., mRNA and protein).
The three types of molecular motors are myosin, kinesin, and dynein
All types of cellular motility are driven by molecular motors that produce unidirectional movement along structural elements in the cell. The structural elements are either filaments composed of actin monomers or microtubules , which are polymers of the protein tubulin. Three distinct types of molecular motors that move along these structures have been described: myosin , kinesin , and dynein . Myosin is a motor that moves along actin filaments. There are many classes of myosins. Myosin II, which is found in all muscles, produces muscle contraction. Myosin V transports vesicles and organelles along actin filaments. Kinesin and dynein transport organelles along microtubules. Kinesins are also involved in spindle formation and chromosome separation during mitosis and meiosis, as well as in mRNA and protein transport. Dyneins mediate the beating of cilia, the movement of flagella, and vesicular trafficking.
Several principles apply to the operation of all molecular motors. Molecular motors convert chemical energy into kinetic energy (movement). The chemical energy is stored in the high-energy phosphate bond of ATP. The motors (myosin, kinesin, and dynein) all have ATPase activity. The binding of ATP, its hydrolysis, and the subsequent release of products are important steps in the generation of movement. In all cases, movement is produced through repetitive cycles of interaction between the motor and either an actin filament or a microtubule. The mechanism whereby ATP hydrolysis is coupled to the conformational and structural changes that produce movement has been elucidated through extensive biochemical, biophysical, and structural studies of muscle contraction and kinesin-based vesicle transport. The mechanism is discussed in a later section.
Single skeletal muscle fibers are composed of many myofibrils
Muscle cell types are classified primarily according to their structural and functional properties. An understanding of the detailed ultrastructure of single muscle cells provides insight into their functional properties. Skeletal muscle cells (skeletal myocytes) are attached to the skeleton by tendons and are under voluntary control. Their primary function is to shorten and generate force to produce movement of skeletal levers. The other two types of muscle, cardiac and smooth, are described later in this chapter.
Skeletal muscle is composed of many individual muscle fibers , each of which is an elongated cell. Each cell is 10 to 100 μm in diameter and may reach several centimeters in length. Electron micrographs reveal that a single skeletal muscle fiber is composed of bundles of filaments, called myofibrils . The myofibrils lie parallel to one another and run along the long axis of the cell ( Fig. 14.1 ). Surrounding each myofibril is an extensive membrane-enclosed intracellular compartment called the SR , which plays a key role in activating muscle contraction. Enlarged portions of the SR, the terminal cisterns, are closely apposed to finger-like invaginations of the sarcolemma (muscle PM) called transverse tubules (T-tubules) ( Fig. 14.1 ). The T-tubule membrane is continuous with the surface membrane. In contrast, the SR membrane is physically distinct, and electrically isolated, from the sarcolemma. The relevance of this point will become clear when we consider the roles of the T-tubule and the SR in excitation-contraction coupling in Chapter 15 . Viewed perpendicular to its long axis, a skeletal muscle cell has a striped appearance, with alternating light and dark bands ( Fig. 14.2 ); this has led to its classification as striated muscle .
The sarcomere is the basic unit of contraction in skeletal muscle
Sarcomeres consist of interdigitating thin and thick filaments
The banding pattern in striated muscle is produced by the regular arrangement of thick and thin filaments in the myofibrils. The light bands are I bands, which contain thin (actin) filaments that extend in both directions from a thin dense line, called the Z line ( Fig. 14.3 ). The region of myofibril between two adjacent Z lines is called a sarcomere . The dark bands, called A bands, contain thick (myosin) filaments arranged in parallel ( Fig. 14.3 ). At the center of the A band is a dense line called the M line. The thin filaments extend into the A bands, but are not present in the central H zone, a
The darker bands are called A bands because they are anisotropic; the I bands are isotropic. Anisotropic material has different refractive indices for different planes of polarized light; isotropic material has a single refractive index. The Z line takes its name from the first letter of Zwischenscheibe (intervening disk, in German). The H in H zone stands for heller (lighter, in German).
which therefore appears lighter. The regular arrangement of thick and thin filaments is clearly shown in a cross section of a myofibril taken in the region of the A band where the filaments overlap ( Fig. 14.3 ). The thick filaments interdigitate with thin filaments so that each thick filament is surrounded by a hexagonal array of thin filaments. This precise filament geometry is maintained by various cytoskeletal proteins that link filaments within a sarcomere and also link the sarcomeres of adjacent myofibrils. One of these important cytoskeletal proteins, α-actinin , is a major component of the Z line structure to which the thin filaments attach. Titin is a giant muscle protein (∼3.8 million daltons) that has an important role in muscle elasticity ( Chapter 16 ). One end of the titin molecule is inserted into the Z line; the other end forms a portion of the thick filament and inserts into the M line.
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