Kinesins motor types

From the marine sponge Haliclona sp. (also known as Adocia sp.), a family of hexaprenoid hydroquinones called adociasulfates, have been recently reported as inhibitors of kinesin motors [100,101], These types of compounds were also found in several soft corals, such as Lemnalia africana [102], Okinawan soft coral of Nephthea sp. [103], and the gorgonian Alertogorgia sp., which yielded the cytotoxic tricyclic sesquiterpene, suberosenone [104],... 

FIGURE 3-23 Motor protein-dependent movement of cargo. The head domains of myosin, dynein, and kinesin motor proteins bind to a cytoskeletal fiber (microfilaments or microtubules), and the tail domain attaches to one of various types of cargo—in this case, a membrane-limited vesicle. Hydrolysis of ATP in the head domain causes the head domain to "walk" along the track in one direction by a repeating cycle of conformational changes. 

FIGU RE 1.7 An expanded mechanochemical cycle of kinesin motors that includes the normal cycle (JF stands for forward cycle. A reversal of T cycle would be the backstep induced by an ATP synthesis) and the possibility of (A) backstep induced by ATP hydrolysis (B) and (B) futile cycle (( )). This type of modification of reaction path is plausible to explain the mechanism of kinesin s backstepping. 

Actin and tubulin are tracks for walking motors powered by nucleotide hydrolysis. These motors fall into three classes myosins, kinesins, and dyneins. The plural applies because, while the force generating principle within each motor type is the same, there is substantial diversity in their dynamical behavior and the cargo they propel. However, the polymer tracks tliemselves probably play only a passive role as highways for intracellular transport. ... 

Interestingly, the dumbbell component of a molecular shuttle exerts on the ring motion the same type of directional restriction as imposed by the protein track for linear biomolecular motors (an actin filament for myosin and a microtubule for kinesin and dynein).4 It should also be noted that interlocked molecular architectures are largely present in natural systems—for instance, DNA catenanes and rotaxanes... 

Vimentin is not the only IF type that is moved in this manner. Neural IFs, including both the type III peripherin proteins and type IV neural IF proteins, have also been demonstrated to be moved by molecular motors. In the case of peripherin, particles and squiggles were observed to translocate rapidly within PCI 2 cell bodies, neurites, and growth cones. The movements were bidirectional and dependent on microtubules, kinesin, and cytoplasmic dynein. The authors suggest that peripherin particles are... 

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.

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...

C-type kinesins have a class-specific neck at the N-terminal side of their motor domain. In the case of DmNcd, the neck forms a continuous a-helix with the less conserved stalk. Constructs of the motor domain with a sufficiently long part of the neck dimerize by formation of a coiled-coil. 

In spite of the gross conformational differences between the Ned dimers, there are only minor differences between the individual motor domains. The overall fold of the motor domain is very similar to that of kinesin-1 and other N-type motors. Major differences are (1) The N-terminal lobe of Ned is enlarged (+9 amino acids) compared with rat kinesin-1. The additional residues are located between /11b and /11c (the L2 finger ). This, however, does not result in a simple elongation of the /1-hairpin as in HsKSP and in M-type motors (see below). In fact, the tip of the L2 finger is rather broadened and forms a short a-helix. (2) Loop L5, the insert in the P-loop helix z 2. is quite short (approximately eight residues compared with 12 in rat kinesin-1), due to three residues that are missing in the primary structure of DmNcd. (3) Switch-1 helix z.3 is short and loop L9, the linker between z.3 and / 6 that includes the switch-1... 

The characteristic feature of the kinesin-13 family is that members of this kinesin family have their motor domain surrounded by N- and C-terminal domains. Therefore, they are also named internal kinesins (KinI) or M-(middle)-type kinesins. The main function of this class of kinesin-related proteins is to target to the ends of microtubules and to induce depolymerization. Although it is not clear whether these proteins display motor activity in a strict sense, it seems appropriate to include them into this review of motor proteins. 

Fast anterograde transport can reach rates as high as 400 mm/day. It is dependent upon microtubules that provide a track along which the vesicles move. The movement is energy dependent and is mediated by a specific motor protein, kinesin. A similar process is responsible for fast retrograde transport. A second motor protein, dynein, is needed for movement in that direction. A third type of transport process is termed slow axoplasmic transport. It ranges from 0.2 to 5 mm/day and is responsible for the transport of cytoskeletal proteins, the neurofilaments, and microtubules, as well as an assortment of cytoplasmic proteins. 

Linear and rotary motors of several types are very common in biology.62 Some examples of linear motors are the myosin-actin complex present in muscles63 or the kinesin-containing systems,64 while examples of rotary motors are provided by the enzyme ATP synthase65 or the motor responsible of mobility of bacterial flagella.66... 

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