Crystal structure of the kinesin motor domain reveals a structural similarity to myosin

Abstract

Kinesin is the founding member of a superfamily of microtubule based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation. It has two identical approximately 960-amino-acid chains containing an amino-terminal globular motor domain, a central alpha-helical region that enables dimer formation through a coiled-coil, and a carboxy-terminal tail domain that binds light chains and possibly an organelle receptor. The kinesin motor domain of approximately 340 amino acids, which can produce movement in vitro, is much smaller than that of myosin (approximately 850 amino acids) and dynein (1,000 amino acids), and is the smallest known molecular motor. Here, we report the crystal structure of the human kinesin motor domain with bound ADP determined to 1.8-A resolution by X-ray crystallography. The motor consists primarily of a single alpha/beta arrowhead-shaped domain with dimensions of 70 x 45 x 45 A. Unexpectedly, it has a striking structural similarity to the core of the catalytic domain of the actin-based motor myosin. Although kinesin and myosin have virtually no amino-acid sequence++ identity, and exhibit distinct enzymatic and motile properties, our results suggest that these two classes of mechanochemical enzymes evolved from a common ancestor and share a similar force-generating strategy.

Structure of the herpes simplex virus 1 capsid with associated tegument protein complexes

“…Beyond its C-terminal helix resolved here, the central one-third of pUL36 also dimerizes to form a coiled-coil helix bundle (57). Intriguingly, this structural organization of the CATC is somewhat reminiscent of cellular motor proteins, which all contain a coiled-coil helix bundle joining their cytoskeleton-binding globular head domains with their cargo-binding domains (58–60). The involvement of CATC in cytoskeleton-dependent α-herpesvirus capsid transport, through either direct or indirect interactions with cellular motor proteins (2–7, 39, 40), now opens the door for new inquiries into the remarkable ability of long-range axonal transport of these neurotropic viruses.…”

Visible Light-Driven Artificial Molecular Switch Actuated by Radical–Radical and Donor–Acceptor Interactions

“…Each 360°rotation of the γ-subunit produces three ATP molecules. Other representative biological molecular machines include myosins, 6,7 kinesins, 8 and bacterial flagella. 9 Inspired by these elegant and sophisticated motors in the biological world, chemists have set about designing and synthesizing 10−20 various primitive nanoscale artificial molecular machines, among which those derived from the mechanically interlocked molecules 21−29 or MIMs for short namely, bistable rotaxanes and bistable catenaneshave emerged as a class of very important frontrunners on account of their highly controllable mechanical motions in response to external stimuli.…”

Nanoscale patterning of kinesin motor proteins and its role in guiding microtubule motility

“…Other biomotors such as dynein move towards the minus end of the microtubules, providing a two way transport system. Conventional kinesin has two heads, each measuring 4 nm×4 nm×7 nm, which use the energy from adenosine triphosphate (ATP) hydrolysis to walk in 8 nm steps along microtubules (Howard 1996;Kull et al 1996;Coy et al 1999). Individual kinesin motors can exert a maximal force of 6 pN (Svoboda et al 1993) and work at efficiencies of ∼50%.…”