Kinesin conventional

Mutations in motor proteins or IFs themselves (which may alter their associations with IFAPs or motors) lead to accumulations of IFs in ALS, Charcot-Marie Tooth disease 2, and Parkinson s (Goldstein and Yang, 2000 Helfand et al., 2004). Impaired assembly and transport of NFs is a critical determinant of neurodegenerative disease. Consistent with a critical role for kinesin in vivo, mice lacking the neuronal-specific conventional kinesin heavy chain KIF5A were shown to have accumulations of NF-H, as well as NF-M and NF-L, in the cell bodies of peripheral sensory neurons. The presence of these accumulations was accompanied by a reduction in... 

Delacruz, J., Brown, J. R., and Langford, G. M. (2003). Interactions between recombinant conventional squid kinesin and native myosin-V. Biol. Bull. 205, 188-190. 

Fig. 1. Domain structures of typical members of the kinesin superfamily. (A) Bar diagram of the kinesin heavy chain (KHC) of conventional kinesin (kinesin-1 family) as a typical representative of N-type motors (motor domain at the N-terminus, red) the cartoon model beneath the bar diagram shows the tetrameric complex of two heavy and two light chains. (B) M-type kinesin like MCAK of the kinesin-13 family. (C) C-type kinesin like Ned of the kinesin-14 family.

The first structure of a kinesin motor domain—that of human kinesin-l (formerly named KHC or conventional kinesin )—was determined by Kull and coworkers (1996). This is still the structure of highest resolution (1.8 A PDB code 1BG2) among all structures of conventional kinesins... 

Fig. 3. Conformation of the switch-2 cluster and neck linker/neck region in various members of the kinesin superfamily. The upper four panels (A, B, E, F) show crystal structures of N-type kinesins with their motor domain at the N-terminus and the neck at the C-terminus. (C), (D), (G), and (H) show C- and M-type kinesins with their neck N-terminal to the motor domain, except for PoKCBP (G) where the C-terminal neck mimic is shown instead of the N-terminal neck (which is not included in the crystal structure). Each structure is shown in two orientations that differ by a rotation of 90 degrees. Rat conventional kinesin (RnKHC [A]) has been chosen to define standard orientations with the neck helix a7 parallel/perpendicular to the drawing area. Orientations for the other structures have been determined by least-squares superposition of their P-loop regions with that of RnKHC (using 11 Ca-atoms of residues F83-T93 in RnKHC). (B), (C), and (D) show the structures of dimeric constructs with the second motor domain in pale colors. The Ned structure in (C) is 180-degree symmetric the symmetry axis is oblique to the drawing plane and coincides with the axis of the coiled-coil that is formed by the two neck helices. In the asymmetric structure of the Ned N600K mutant (D), the second motor domain (pale) is rotated by about 75 degrees around an axis perpendicular to the coiled-coil. The structures shown in (A), (B), (F), and (G) have their switch-2 cluster in permissive conformation, whereas the conformation of structures (C), (D), (E), and (H) is obstructive, as can be told by observing the slope of the extended switch-2 helix a4. Color code red, switch-2 cluster including the extended...

Kozielski, F., Svergun, D., Zaccai, G., Wade, R. H., and Koch, M. H. (2001). The overall conformation of conventional kinesins studied by small angle x-ray and neutron scattering. / Biol. Chem. 276, 1267-1275. 

Auerbach SD, Johnson KA. Alternating site ATPase pathway of rat conventional kinesin. J. Biol. Chem. 2005 280 37048-37060. 

Figure 34.7. Kinesin at Low Resolution. An electron micrograph of conventional kinesin reveals an elongated structure with two heads at one end. The position of the light chains was confirmed through the use of antibody labels. [After N. Hirokawa, K. K. Pfister, H. Yorifuji, M. C. Wagner, S. T. Brady, and G. S. Broom. Cell 56 (1989) 867.]...

Figure 34.26. Structure of Ned. The head domain of ned is quite similar to that of conventional kinesin, including the presence of a P-loop NTPase domain (shaded in purple). In the ADP form of ned (shovm), the amino-terminal part of this fragment forms an a-helix that docks into the site occupied by the neck linker in the ATP form of conventional kinesin.

Designer kinesins. Hybrids of kinesin have been prepared that consist of either (a) the sequence of conventional kinesin with the motor domain replaced by that of ncd or (b) the sequence of ncd with the motor domain replaced by that of conventional kinesin. In which direction along microtubules would you predict these hybrid kinesins to move ... 

The first (a) should behave like conventional kinesin and move toward the plus end of microtubules, whereas the second (b) should behave like ncd and move toward the minus end. 

Figure 34.27 suggests that the choice of direction is determined by the neck and stalk domains and not by the motor domains. Therefore, it is reasonable to predict that (a) conventional kinesin with a motor domain from ncd will continue to move in the plus direction (characteristic of kinesin), whereas (b) ncd protein with a motor domain from kinesin veill move in the minus direction (characteristic of ncd). (Nevertheless, single mutations within the chimeric constructs are able to reverse the direction, suggesting that the regulatory mechanisms are complex see Science 281 [1998] 1200.)... 

FIGURE 1.1 (See color insert following page 172.) Kinesin and microtubule. (A) Conventional kinesins are homodimer, each of the monomer is made of head, neck-linker, and neck-helix domain. The neck-linkers of two heads are colored in green and yellow, respectively. The neck-helices from the two monomers associate the two subunits. (B) A microtubule with 13 protofilaments, each of which is made of an 8nm periodic head-to-taU alignment of the tubulin dimer subunits. A single protofilament that is used as a track for kinesin is colored in red. Kinesins take steps hand-over-hand along the protofilament. 

Neck-length djd.2 (nm) Conventional kinesin 5.2/4.7 (unwinding/ rewinding state)... 

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