Kinesins conformational switching

IV. Conformational Switching in Kinesin A. Comparison with Myosin... 

Structural Alignment of the Switch-1 and Switch-2 Regions of Kinesin Motor Domains with Secondary Structure Assignments and Classification of the Switch-2 Cluster and Neck/Neck Linker Conformations... 

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...

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... 

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