Motor domains

Smith, C. A., Rayment, 1. X-ray structure of the magnesium (11). ADP-vanadate complex of the Dictyostelium discoideum myosin motor domain to 1.9 A resolution. Biochemistry 35 5404-5407, 1996. 

Fisher, A., Smith, C., Thoden, J., et al., 1995. X-ray structures of die myosin motor domain of Dietyostelium diseoideumcomplexedMth MgADP BeFx and MgADP AlF4. Biochemistry 34 S960-S972. 

Hirose, K, Lockhart, A., Cross, R., and Amos, L., 1995. Nncleodde-depen-dent angnlar change in kinesin motor domain bound to tnbnlin. Nature 376 277-279. 

Knll, F. J., Sablin, E. P, Lan, R., et al., 1996. Crystal structure of die kinesin motor domain reveals a structural similarity to myosin. Nature 380 550-555. 

Motor proteins move along MTs in an ATP-dependent manner. Members of the superfamily of kinesin motors move only to the plus ends and dynein motors only to the minus ends. The respective motor domains are linked via adaptor proteins to their cargoes. The binding activity of the motors to MTs is regulated by kinases and phosphatases. When motors are immobilized at their cargo-binding area, they can move MTs. 

Systematic cloning strategies based on the conserved motor domain sequences have identified a remarkable number of KRPs expressed in brain. Members of several KRP families expressed in brain have been implicated in forms of MBO transport. Kinesin-2 family members have been implicated in assembly and maintenance of cilia and... 

Although the last family of motor proteins to be discovered, the kinesins have proved to be remarkably diverse. So far, there are at least 14 distinct subfamilies in the kinesin family and more are likely to emerge, all with homology in their motor domain [53], Within a subfamily, however, the more extensive sequence similarities are presumed to reflect related functions. At present, many questions remain about the function of these various motors in the nervous system. 

A myosin head is made up of 850 residues, but the motor domain of a kinesin contains only -345. Like... 

Fig. 19-4).212b However, single kinesin heads, which lack the coiled-coil neck region, have a duty ratio of <0.45. The movement is nonpro-cessive.213 The Ned motor is also nonprocessive.214-216 As mentioned previously, the Ned and kinesin motor domains are at opposite ends of the peptide chain, and the motors move in opposite directions along microtubules.217 218 The critical difference between the two motor molecules was found in the neck domains, which gave rise to differing symmetries in the two heads.219 The latter are shown in Fig. 19-20, in which they have been docked onto the tubulin protofilament structure.

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... 

Gulick, A. M., Bauer, C. B., Thoden, J. B., and Rayment, I. (1997). X-ray structures of the MgADP, MgADPgammaS, and MgAMPPNP complexes of the Dictyostelium discoideam myosin motor domain. Biochemistry 36, 11619-11628. 

Ruppel, K. M., and Spudich, J. A. (1996). Structure-function analysis of the motor domain of myosin. Annu. Rev. Cell Dev. Biol. 12, 543-573. 

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).

Fig. 16. (A) Myosin head SI showing the two domains referred to as the motor domain...

Dominguez, R., Freyzon, Y., Trybus, K. M., and Cohen, C. (1998). Crystal structure of a vertebrate smooth muscle myosin motor domain and its complex with the essential light chain Visualization of the pre-power stroke state. Cell 94, 559-571. 

For the outline in Scheme 3, two situations can be considered the isometric case where a large load attached to the myosin lever-arm prevents the lever-arm from completing its swing, and the unloaded situation as seen in solution for a single motor domain. 

Kovacs, M., Malnasi-Csizmadia, A., Woolley, R. J., and Bagshaw, R. J. (2002). Analysis of nucleotide binding to Dictyostelium myosin II motor domains containing a single tryptophan near the active site./. Biol. Chem. 277, 28459-28467. 

Hirose, K., Fan, J., and Amos, L. A. (1995a). Re-examination of the polarity of microtubules and sheets decorated with kinesin motor domain. J. Mol. Biol. 251, 329-333. 

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