Kinesins domains

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. 

Hirokawa, N., Pfister, K.K., Yorifuji, H., Wagner, M.C., Brady, S.T., Bloom, G.S. (1989). Sub-molecular domains of bovine brain kinesin identified by electron microscopy and monoclonal antibody decoration. Cell 56, 867-878. 

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. 

KISc Kinesin motor, catalytic domain, ATPase E(MFP) 6(6) 20(20) 2NCD... 

Mapping the kinesin KIF5C Interaction domain of GRIF-1 using a modified LEXA yeast two-hybrid... 

Brickley K, Smith MJ, Beck M, Stephenson FA. 2005. GRIF-1 and OIP106, members of a novel gene family of coiled-coil domain proteins association in vivo and in vitro with kinesin. J Biol Chem 280 14723-14732. 

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.

The modular design of kinesin motors is nicely illustrated by switching domains between the kinesin arid Ned motors.90 Kinesin moves unidirectionally to one end of microtubules (the plus end), whereas Ned moves in the opposite direction. Replacing the catalytic domain of kinesin with that of Ned gives a motor that still moves in the kinesin direction. Kinesin is highly processive, remaining attached to a single filament (see Chapter 14, section A7), The Ncd-kinesin chimera has the lower processivity of Ned. 

The characteristic (consensus) sequence ofP-loops (the Walker A motif Walker et al., 1982) is Gly-x-x-x-x-Gly-Lys-Thr/Ser (the region in red in Fig. 5) this sequence is often used in bioinformatic searches to identify proteins related to this family. Each myosin and kinesin has a single P-loop. For example, Dictyostelium myosin II has the sequence as in Fig. 5 (179) G-E-S-G-A-G-K-T (186). On the other hand, dynein, with a heavy chain that partly forms a ringlike core complex of six AAA+ domains, has P-loop motifs in the first four of these domains (e.g., G-P-A-G-P-G-K-T). There may be a complex series of interactions between these various sites to generate movement, but the P-loop in the third domain has been shown to be essential for dynein motor function (Silvanovich et al., 2003). 

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... 

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. 

Microtubules are the intracellular tracks for two classes of motor proteins kinesins and dyneins. During the past few years, the motor domain structures of several kinesins from different organisms have been determined by X-ray crystallography. Compared with kinesins, dyneins are much larger proteins and attempts to crystallize them have failed so far. Structural information about these proteins comes mosdy from electron microscopy. In this chapter, we mainly focus on the crystal structures of kinesin motor domains. 

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