Myosin heads, structure

Approximately 500 of the 820 amino acid residues of the myosin head are highly conserved between various species. One conserved region, located approximately at residues 170 to 214, constitutes part of the ATP-binding site. Whereas many ATP-binding proteins and enzymes employ a /3-sheet-a-helix-/3-sheet motif, this region of myosin forms a related a-f3-a structure, beginning with an Arg at (approximately) residue 192. The /3-sheet in this region of all myosins includes the amino acid sequence... 

The myosin head has long been shown to induce, even in low ionic strength buffers, polymerization of G-actin into decorated F-actin-S i filaments that exhibit the classical arrowhead structure (Miller et al., 1988 and older references therein). However, to date, the molecular mechanism of this polymerization process remains unknown. 

Figure 19-12 (A) Stereoscopic views of computer-assisted reconstructions of images of myosin heads attached to an F-actin filament centered between two thick filaments. Atomic structures of actin (Fig. 7-10) and of myosin heads (Fig. 19-15) have been built into the reconstructed images obtained by electron microscopy. (A) With the nonhydrolyzable ATP analog ATPPNP bound in the active sites. (B) Rigor. Two myosin heads are apparently bound to a single actin filament in (A). If they belong to the same myosin molecule the two C-terminal ends must be pulled together from the location shown here. In (B) a third head is attached, presumably from another myosin rod. This configuration is often seen in rigor. From Winkler et al.13i Courtesy of K. A. Taylor.

Steps in the contraction process. Because contraction is a cyclical process, the choice of a starting point is somewhat arbitrary. Five frames are shown the first two and the last two frames are identical to make the cyclical nature of the process clear. In the first frame (a), the myosin head groups contain the hydrolysis products of a single ATP molecule, ADP and P . A structural transition in the actin leads to contact between the actin and the myosin and the release of P,. 

In the second frame (b), strong bridges form between actin and myosin. This is followed by a structural alteration in the myosin molecules and an effective translocation of the thick filament relative to the thin filament in (c). During this process the ADP is released. After the translocation step, the bridge structure is broken by the binding of ATP, which is rapidly hydrolyzed to ADP and Pj. Each thick filament has about 500 myosin heads, and each head cycles about five times per second in the course of a rapid contraction. 

Examining these structures and the fact that they are all powered by ATP, the question remains as to how force is actually produced. Geeves and Holmes (2005) argue that myosin acts by the specific coupling between different myosin head states and different positions of the lever arm on the motor domain, so that, once attached to actin, the myosin acts as an ATP-driven motor where the energy released by ATP hydrolysis is direcdy coupled to the performance of mechanical work. However, Marx et al. (2005) argue that in some cases the kinesins appear to act as thermal ratchets. In this case, the attachment of a second head, once the first head has bound, is an event controlled by thermal motion, but, presumably for steric reasons, the head is more likely to bind to the microtubule in the... 

Studies of the myosin head, the globular part of the heavy chain together with the ELC and RLC, were dramatically transformed when the isolated myosin head from chicken skeletal muscle myosin was crystallized and its structure solved using protein crystallography by Rayment et al. (1993b Fig. 4A). This showed that the head consists of a globular... 

As in the case of the myosin head, knowledge of actin filament structure, or thin filament structure as it is termed when tropomyosin and troponin are present, also progressed rapidly when the structure of the globular actin (G-actin) monomer was determined by protein crystallography in... 

One of the tasks of structural biologists studying muscle contraction is to determine the organization and shapes of the myosin head in muscle under different physiological conditions. The technique of low-angle X-ray diffraction has unique advantages in this process, particularly since it can be applied to living muscle, which can be stimulated to produce active force or can be studied under a variety of different steady-state conditions. The main problem with X-ray fiber diffraction, as detailed in Squire and... 

Fig. 15. Stereo views of the different myosin head, SI, structures showing their variable conformations in different crystal structures. (A) The heads with their motor domains superimposed and oriented as if interacting with a vertical actin filaments in the rigor conformation, Z-band bottom and M-band top. (B) The same structures in a view down the actin filament long axis, looking from the M-band towards the Z-band. Blue is the Dominguez et al. (1998) structure of SI in chicken smooth muscle with ADP.AIF4 bound, orange is the insect flight muscle SI in the ADP.Pj state (Al-Khayat et al., 2003), yellow is scallop SI crystal structure in the ADP.VO4 state (Houdusse et al., 1999), and green is the chicken skeletal muscle with no nucleotide bound (Rayment et al., 1993a).

Houdusse, A., Kalabokis, V. N., Himmel, D., Szent-Gyorgyi, A. G., and Cohen, C. (1999). Atomic structure of scallop myosin subfragment SI complexed with MgADP A novel conformation of the myosin head. Cell 97, 459-470. 

---