BIOCHEMISTRY - L. Stryer - 1984

VOLUME 3

PART V. MOLECULAR PHYSIOLOGY

CHAPTER 34. MUSCLE CONTRACTION AND CELL MOTILITY

Summary

Vertebrate striated Muscle consists of Two Types of protein filaments that interact with one another. Thick filaments contain Myosin, whereas thin filaments contain Actin, Tropomyosin, and troponin. The Hydrolysis of ATP by Actomyosin causes these filaments to slide past one another. Myosin is a very large protein (500 kDa) composed of two heavy chains and four light chains. The conformation of the heavy chains includes two globular domains (S1 heads) and a long α-helical tail attached to them. The S1 heads and part of the tail form cross-bridges that interact with actin to generate contractile force. The remainder of the myosin molecule forms the backbone of the thick filament. Actin, the primary component of thin filaments, is a globular protein (42 kDa) that polymerizes to form filaments 70 A in diameter. Thick and thin filaments have a defined polarity, which reverses direction at the

midpoint between two Z discs. The cyclic formation and dissociation of complexes between myosin cross-bridges projecting from the thick filaments and actin units of the thin filaments are driven by the energy of ATP; complex formation leads to a shortening of the distance between Z discs. The "power stroke" is the Rotation of the myosin S1 HEAD complexed with actin. Hinged regions between the domains of myosin play a crucial role in generating contractile force. Muscle contraction is regulated by Ca²⁺, with The Effect of Ca²⁺ being mediated by troponin and tropomyosin. At low Ca²⁺ concentrations, these Proteins inhibit the interaction between Actin and myosin. A Nerve Impulse triggers the release of Ca²⁺ from the sarcoplasmic reticulum. Calcium Ions then bind to troponin, initiating a series of conformational shifts that ultimately permit the interaction of actin and myosin.

Class="center">Fig. 34.33. Dynein arms are arranged along microtubules with a regular periodicity. Cytology/cytology/93.html">ELECTRON MICROGRAPHS OF an intact axoneme (A) and a microtubule reconstructed from tubulin and dynein (B)

Fig. 34.34. Inner surface of a fibroblast Cell/33.html">Plasma Membrane as seen under an Electron microscope. Actin filaments (decorated with myosin S1 heads) and coated pits on the membrane are clearly visible

Actin and myosin are evolutionarily ancient proteins, as evidenced by the fact that they are already present in slime Molds. In essence, these proteins participate in the contractile activity of virtually all Eukaryotic Cells. Actin is especially widespread, forming microfilaments about 70 A in diameter. Microfilaments are involved in Various Forms of cell motility, such as cell migration during development, Blood clot retraction by platelets, and macrophage locomotion toward damaged sites. The contraction of intestinal epithelial microvilli is mediated by the interaction of actin filaments with bipolar myosin filaments; the latter are smaller and present in a lower relative Abundance in intestinal epithelial cells compared to muscle. Cytochalasin and phalloidin inhibit forms of cell motility that depend on the assembly and disassembly of actin filaments. Cytochalasin inhibits assembly, whereas phalloidin inhibits The breakdown of microfilaments.

Eukaryotic cells contain microtubules, which maintain cellular architecture and also participate in contractile activity. Microtubules are hollow fibrils 240 A in diameter, constructed from tubulin. Eukaryotic Cilia and flagella contain nine double microtubules surrounding two

single ones. Cross-bridges composed of dynein, a protein with ATPase activity, span the space between the outer pairs of microtubules. Dynein-induced sliding of adjacent microtubule pairs relative to one another causes the cilium or flagellum to bend; this mechanism underlies ciliary beating and flagellar movement. Colchicine serves as an inhibitor of microtubule-mediated motility by blocking their polymerization.