Myosin chains

The muscle proteins myosin and tropomyosin also both consist of pairs of identical chains oriented in the same direction. The two 284-residue tropomyosin chains each contain 40 heptads and are linked by a single disulfide bridge. X-ray crystallographic studies and electron microscopy show tiiat the molecule is a rod of 2.0 nm diameter and 41 nm length, the dimensions expected for the coiled coil. However, as with other regular" protein structures, there are some irregularities. Myosin chains (Chapter 19) contain 156 heptads. 

Vomiting and diarrhea have been recorded in many cases of human intoxication ascribed to palytoxin, along with paresthesia of the extremities. In fatal cases, respiratory distress and cyanosis preceded death. In most of the reports listed in Table 32.8, there is evidence for muscle damage in humans, as indicated by myalgia, myoglobinuria, and elevated serum activities of muscle-derived enzymes and light myosin chain. 

Myoglobinuria. Elevated serum activities of creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. Increased serum level of light myosin chain. Serum urea and creatinine levels normal... 

The structures used here contain that part of the amino terminus of myosin (residues 1 to 835) just sufficient to include the essential and regulatory light chains. Thus, the cross-bridge is composed of three chains—approximately 800 residues from the amino terminus of the myosin chain, the essential light chain, and the regula-... 

By selecting specific muscle types the authors were able to separate different myofibrillar protein types slow-contracting, fast-contracting and heart. Since each muscle fibre type contains its own specific myosin chain, the gelation properties of fractions prepared from them vary. In fact, most muscles contain a mixture of both types of myosin, as well as a third (fast-contracting) type. Salt was required to produce gels however, once... 

No detailed information has been obtained as yet about the nature of the combining groups of actin and myosin. There are about 0.1 g of myosin and 0.04 g of actin in 1 cm" of muscle, corresponding to 0.6 x 10 mole of myosin chains (three per molecule) and 0.7 X 10 mole of actin molecules. The approximate agreement of these numbers supports the reasonable assumption of one combining region per myosin chain and per actin molecule. 

In the presence of calcium, the primary contractile protein, myosin, is phosphorylated by the myosin light-chain kinase initiating the subsequent actin-activation of the myosin adenosine triphosphate activity and resulting in muscle contraction. Removal of calcium inactivates the kinase and allows the myosin light chain to dephosphorylate myosin which results in muscle relaxation. Therefore the general biochemical mechanism for the muscle contractile process is dependent on the avaUabUity of a sufficient intraceUular calcium concentration. 

Alpha helices are sufficiently versatile to produce many very different classes of structures. In membrane-bound proteins, the regions inside the membranes are frequently a helices whose surfaces are covered by hydrophobic side chains suitable for the hydrophobic environment inside the membranes. Membrane-bound proteins are described in Chapter 12. Alpha helices are also frequently used to produce structural and motile proteins with various different properties and functions. These can be typical fibrous proteins such as keratin, which is present in skin, hair, and feathers, or parts of the cellular machinery such as fibrinogen or the muscle proteins myosin and dystrophin. These a-helical proteins will be discussed in Chapter 14. 

Fibrous proteins can serve as structural materials for the same reason that other polymers do they are long-chain molecules. By cross-linking, interleaving and intertwining the proper combination of individual long-chain molecules, bulk properties are obtained that can serve many different functions. Fibrous proteins are usually divided in three different groups dependent on the secondary structure of the individual molecules coiled-coil a helices present in keratin and myosin, the triple helix in collagen, and P sheets in amyloid fibers and silks. 

Figure 14.14 Sci ematic diagram of the myosin molecule, comprising two heavy chains (green) that form a coiled-coil tail with two globular heads and four light chains (gray) of two slightly differing sizes, each one bound to each heavy-chain globular head.

Figure 14.15 Stmcture of the SI fragment of chicken myosin as a Richardson diagram (a) and a space-filling model (b). The two light chains are shown in magenta and yellow. The heavy chain is colored according to three proteolytic fragments produced by trypsin a 25-kDa N-terminal domain (green) a central 50-kDa fragment (red) divided by a cleft into a 50K upper and a 50K lower domain and a 20-kDa C-terminal domain (blue) that links the myosin head to the coiled-coil tail. The 50-kDa and 20-kDa domains both bind actin, while the 25-kDa domain binds ATP. [(b) Courtesy of 1. Rayment.]...

Fibrous proteins are long-chain polymers that are used as structural materials. Most contain specific repetitive amino acid sequences and fall into one of three groups coiled-coil a helices as in keratin and myosin triple helices as in collagen and p sheets as in silk and amyloid fibrils. 

Myosin light-chain kinase (MLCK) —ia[Pg.467]

Smooth muscle contractions are subject to the actions of hormones and related agents. As shown in Figure 17.32, binding of the hormone epinephrine to smooth muscle receptors activates an intracellular adenylyl cyclase reaction that produces cyclic AMP (cAMP). The cAMP serves to activate a protein kinase that phosphorylates the myosin light chain kinase. The phosphorylated MLCK has a lower affinity for the Ca -calmodulin complex and thus is physiologically inactive. Reversal of this inactivation occurs via myosin light chain kinase phosphatase. 

The ETa receptor activates G proteins of the Gq/n and G12/i3 family. The ETB receptor stimulates G proteins of the G and Gq/11 family. In endothelial cells, activation of the ETB receptor stimulates the release of NO and prostacyclin (PGI2) via pertussis toxin-sensitive G proteins. In smooth muscle cells, the activation of ETA receptors leads to an increase of intracellular calcium via pertussis toxin-insensitive G proteins of the Gq/11 family and to an activation of Rho proteins most likely via G proteins of the Gi2/i3 family. Increase of intracellular calcium results in a calmodulin-dependent activation of the myosin light chain kinase (MLCK, Fig. 2). MLCK phosphorylates the 20 kDa myosin light chain (MLC-20), which then stimulates actin-myosin interaction of vascular smooth muscle cells resulting in vasoconstriction. Since activated Rho... 

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