Kinesins are eukaryotic microtubule-associated motor proteins (also called mechanochemical proteins) which convert chemical energy released from nucleoside triphosphates (preferentially from ATP) into mechanical energy.
last decade, numerous kinesin isoforms and related proteins, sharing a common
motor domain of 340-350 amino acids (see Sakowicz et al., 1998; Stewart et
al., 1993), have been described in animal and plant cells as well as in
lower eukaryotic organisms, e.g., yeast and Aspergillus (for reviews
see Goodson et al., 1994, Vale and Fletterick, 1997, Hirokawa, 1998).
A prominent member of the kinesin superfamily, currently including more than 600 sequences from a variety of species (see Marx et al. 2005), is the conventional kinesin (kinesin-1, see recent nomenclature published by LAWRENCE et al. 2004), which essentially contributes to anterograde vesicle transport in neuronal cells (Schnapp et al., 1992). It is a plus end-directed molecular motor, whose ATPase is strongly promoted by microtubules (Kuznetsov and Gelfand, 1986; Huang and Hackney, 1994).
Dreblow K., Böhm KJ,: Mechanism of kinesin-dependent vesicle transport along a microtubule
(Copyright 2009. All rights reserved by the authors)
Kinesin-1 is a dimer (Hirose and Amos, 1999) consisting of two identical 120 to 130-kDa chains, commonly known as heavy chains. When kinesin is purified from brain homogenates, two light chains (60 to 70 kDa) were found to be associated with the dimers (Kull 2000). These light chains, which are involved in the kinesin binding to organelles, are not essential for motility generation (Howard 1997) and seem to have regulatory functions ((Verhey et al., 1998).
comprises three distinct domains: the N-terminal motor domain, the central
stalk domain, and the C-terminal fan-shaped tail, which is (presumably
together with the stalk) implicated in cargo binding.
The motor domain, which is known to be a highly conserved region characteristic for very different members of the kinesin superfamily, can be subdivided into the core motor domain, the adjacent neck linker and the neck region.
Its core domain, consisting of about 325 amino acids, contains both the microtubule-binding and the ATPase-active sites (Kull 2000).
The stalk region is described to be responsible for dimerization.
Kinesin dimer (for a detailed scheme see Woehlke and Schliwa 2000)
The kinesin head domain has the shape of an arrow head with dimensions of approximately 7.5 nm x 4.5 nm x 4.5 nm. X-ray structural analysis revealed a central, eight-stranded beta-sheet with three alpha-helices on either side (Kull et al. 1996; Sack et al. 1997).
A characteristic feature of the two-headed kinesin-1 is its processivity, i.e., single kinesin molecules move along microtubules of several micrometers length without dissociating (Block et al., 1990; Crevel et al., 1997; Hancock and Howard, 1998). Both heads translocate by turns in 16-nm steps, resulting in an 8-nm centre-of-mass migration (Mandelkow and Johnson, 1998), one of them is always bound to the microtubule (Ray et al., 1993; Kozielski et al., 1998). Recently, it has been shown that also one-headed members of the kinesin superfamily, e.g., KIF1A, can realize movement in a processive fashion. This was explained by the existence of two microtubule-binding motifs in one head (Schief and Howard, 2001).
Intracellular movement and transport processes can be mimicked in vitro either by gliding of taxol-stabilized microtubules across kinesin-coated glass surfaces (Vale et al., 1985; von Massow et al., 1989; Schnapp et al., 1990) or by translocation of kinesin-coated polymer beads along immobilized microtubules (Kuo et al., 1991).
Microtubule gliding across a kinesin-coated glass surface (Copyright 2009. K. Dreblow, KJ. Böhm, FLI Jena) Video sequence of microtubules gliding across kinesin-coated glass surface
The velocity of motility generated by kinesin-1 is typically found between 0.4 µm/s and 0.9 µm/s (Vale et al., 1985; von Massow et al., 1989, Steinberg and Schliwa 1996, Böhm et al., 1997). For comparison, a kinesin from the fungus Neurospora was found to walk at velocities up to 3.8 µm/s (Steinberg and Schliwa 1996). In contrast, the mitotic kinesin Eg5 moves at about 0.06 µm/s, only (Lockhart and Cross 1996). For kinesin-1 it was shown that microtubule gliding can be accelerated by increasing the Mg2+ concentration at a constant ATP concentration (Böhm et al. 2000a) and by temperature elevation (Böhm et al. 2000b). At high temperatures velocities up to 3.7 µm/s were measured (Kawaguchi and Ishiwata 2001).
Microtubule gliding across a kinesin-coated glass surface in the presence of 5.0 M glycerol
In the presence of glycerol or other polyhydroxy compounds, a remarkable fraction of the microtubules gliding across a kinesin-coated glass surface did not follow a straight line but circular tracks (Böhm et al. 2001).
Further information on kinesin and
other cytoskeleton motor proteins can be obtained from our recent review on
Kinesin and nanoactuators. (Böhm
KJ, Unger E,
See also the recent review of Marx A, Muller J, Mandelkow E.: The structure of microtubule motor proteins. Adv Protein Chem. 71 (2005) 299-344.
BLOCK SM, GOLDSTEIN LS, SCHNAPP BJ, 1990.
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Böhm KJ, Stracke R, Unger E, 2000a. Speeding up kinesin-driven microtubule gliding in vitro by variation of cofactor composition and physicochemical parameters. Cell Biol. Int., 24, 335-341.
Böhm KJ, Stracke R, Baum M, Zieren M, Unger E, 2000b. Effect of temperature on kinesin-driven microtubule gliding and kinesin ATPase activity. FEBS Letters 466, 59-62.
Böhm KJ, Stracke R, Vater W, Unger E, 2001: Inhibition of kinesin-driven microtubule motility by polyhydroxy compounds. In: Micro- and Nanostructures of Biological Systems (eds. Hein H-J, Bischoff G) Shaker Verlag Aachen, pp. 153-165 (2001)
Böhm KJ, Unger E, 2004. Kinesin and nanoactuators. In: Encyclopedia of Nanoscience and Nanotechnology (ed. Nalwa, HS) American Scientific Publishers vol. 4, pp. 345-357
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