Myosin

Myosin (Fig. 10.13) is a rather complex molecule with a molecular weight of about 470000. It is made up of six polypeptide chains, two long ones (heavy chains) and four short ones (light chains). Electron microscopy of isolated molecules shows that they consist of two 'heads' attached to a long 'tail'. The two heavy chains wind round each other to form the tail region, but they separate to form the two heads. The light chains, of two types called the essential and regulatory light chains, form part of the heads.

A most important property of myosin is that it is an ATPase, i.e. it acts as an enzyme to hydrolyse ATP, forming ADP and inorganic phosphate. Treatment with the proteolytic enzyme trypsin splits the myosin molecule into two sections known as light meromyosin and heavy meromyosin; only heavy meromyosin acts as an ATPase. Electron microscopy shows that

Fig. 10.13. The six polypeptide chains that form the myosin molecule. The whole molecule consists of two globular heads attached to a long tail. The tail or rod is a coiled-coil formed from the a-helical regions of the two heavy chains; it is divided into an LMM (light meromyosin) section, and an S2 (subfragment 2) section. Each heavy chain has a globular region that combines with two light chains to form an S1 head. The light chains are of two types, called essential (ELC) and regulatory (RLC). Heavy meromyosin (HMM) consists of the S1 and S2 subfragments. Enzymic activity and the molecular motor are found in the S1 heads. LMM aggregates with others to form the backbone of the myosin filament, and the S2 part of the rod connects it to the two S1 heads. Reprinted from Trends in Biochemical Sciences, vol. 19, I. Rayment & H. M. Holden, The three-dimensional structure of a molecular motor, p. 129, copyright 1994, with permission from Elsevier Science.

Fig. 10.13. The six polypeptide chains that form the myosin molecule. The whole molecule consists of two globular heads attached to a long tail. The tail or rod is a coiled-coil formed from the a-helical regions of the two heavy chains; it is divided into an LMM (light meromyosin) section, and an S2 (subfragment 2) section. Each heavy chain has a globular region that combines with two light chains to form an S1 head. The light chains are of two types, called essential (ELC) and regulatory (RLC). Heavy meromyosin (HMM) consists of the S1 and S2 subfragments. Enzymic activity and the molecular motor are found in the S1 heads. LMM aggregates with others to form the backbone of the myosin filament, and the S2 part of the rod connects it to the two S1 heads. Reprinted from Trends in Biochemical Sciences, vol. 19, I. Rayment & H. M. Holden, The three-dimensional structure of a molecular motor, p. 129, copyright 1994, with permission from Elsevier Science.

heavy meromyosin has two 'heads' and a short 'tail', whereas light meromyosin is a rod-like molecule. Heavy meromyosin can be further split by digestion by papain, to give two globular S1 subfragments (the 'heads') and a short rod-like S2 subfragment. The ATPase activity is confined to the S1 subfragment. Light meromyosin molecules will aggregate to form filaments under suitable conditions, but neither heavy meromyosin nor its two subfragments will.

H. E. Huxley found that under the right conditions myosin molecules can aggregate to form filaments. These filaments have regularly spaced projections on them which almost certainly correspond to the projections and cross-bridges seen in thin sections of myofibrils. In the middle of each filament is a section from which these projections were absent, which must correspond to the L zone of intact muscle fibres. Similar filaments could be isolated from homogenised myofibrils; they were all 1.6 fxm long, whereas the 'artificial' filaments were variable in length. Huxley suggested that the 'tails' of the myosin molecules become attached to each other to form a filament as shown in Fig. 10.14, with the 'heads' projecting from the body of the filament. Notice

Fig. 10.14. How the myosin molecules assemble to form a thick filament with a projection-free shaft in the middle and reversed polarity of the molecules in each half of the sarcomere. From Bagshaw (1993), Muscle Contraction, Fig. 4.7, p. 43, with kind permission from Kluwer Academic Publications.

particularly that this arrangement accounts for the bare region in the middle, and also that it implies that the polarity of the myosin molecules is reversed in the two halves of the filament.

X-ray diffraction studies show that there is an axial repeat of 14.3 nm and a helical repeat of 42.9 nm on the myosin filament, as has already been mentioned. This suggests that a group of myosin heads emerges from the filament every 14.3 nm, and that their orientation rotates so that every third group is in line. There are probably three myosin molecules in each group, as is suggested in Fig. 10.15a.

The amino acid sequence of the myosin heavy chain suggests that the whole of the tail section of the molecule is a-helical in structure, with the two heavy chains coiled round each other. The S1 head has a much less regular structure. X-ray diffraction studies by Rayment and his colleagues show that the head is divided into various functional regions: an actin-binding site, an ATP-binding site, and a lever arm about 10 nm long, which connects to the S2 link (see Fig. 10.17). The light chains are associated with the lever arm section of the S1 head.

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