X-ray Structure of Motor and Neck Domains from Rat Brain Kinesin^,

Abstract

We have determined the X-ray structure of rat kinesin head and neck domains. The folding of the core motor domain resembles that of human kinesin reported recently [Kull, F. J., et al. (1996) Nature 380, 550-554]. Novel features of the structure include the N-terminal region, folded as a beta-strand, and the C-terminal transition from the motor to the rod domain, folded as two beta-strands plus an alpha-helix. This helix is the beginning of kinesin's neck responsible for dimerization of the motor complex and for force transduction. Although the folding of the motor domain core is similar to that of a domain of myosin (an actin-dependent motor), the position and angle of kinesin's neck are very different from those of myosin's stalk, suggesting that the two motors have different mechanisms of force transduction. The N- and C-terminal ends of the core motor, thought to be responsible for the directionality of the motors [Case, R. B., et al. (1997) Cell 90, 959-966], take the form of beta-strands attached to the central beta-sheet of the structure.

Minimal Models for Proteins and RNA: From Folding to Function

“…127,128 The structural studies using X-ray crystallography [129][130][131] and cryo-EM 132,133 structures show that the kinesin motor has two heavy chains and two light chains. The heavy chain has a globular head (the motor domain) connected via a short, flexible neck linker to the stalk, which is a long, coiled-coil region that ends in a tail region formed with a light-chain.…”

Orphan Kinesin NOD Lacks Motile Properties But Does Possess a Microtubule-stimulated ATPase Activity

“…Moreover, all five of these divergent kinesins lack the conserved glutamate located six amino acids C-terminal to the position where the second conserved arginine should be. This glutamate has been found to stabilize the second arginine via a salt bridge Sablin et al, 1996;Sack et al, 1997). Moreover, the microtubule-depolymerizing Ikins, at least some of which also lack demonstrable in vitro motility (Desai et al, 1999), have a charged residue in the X position, as does NOD.…”

“…Sequence analysis indicates that NOD lacks a neck region (Vale and Fletterick, 1997) and also lacks the critical neck interacting residues (LGG) of the catalytic core as well (Figure 1, L13) (Sack et al, 1997;Sablin et al, 1998;Case et al, 2000). The replacement of the more flexible GG with TA in NOD may hinder the nucleotide-dependent conformational changes observed in other kinesins.…”

Kinesin motors as molecular machines

“…(41) Although the neck linker was disordered in the first crystal structure of a kinesin motor, (42) presumably due to its mobility in the crystal lattice, subsequent crystal structures show a visible neck linker consisting of two b-strands that interact with other b-strands of the motor domain. (41,43) The mobile or undocked conformation of the neck linker is thought to alternate with docking against the motor core. Undocking of the neck linker would not only potentially enable the two heads of dimeric conventional kinesin to reach between two adjacent binding sites along the microtubule, but could also amplify a small movement of the motor core, producing a power stroke.…”