Abstract
Success of mitosis depends upon the coordinated and regulated activity of many cellular factors, including kinesin motor proteins, which are required for the assembly and function of the mitotic spindle. Eg5 is a kinesin implicated in the formation of the bipolar spindle and its movement prior to and during anaphase. We have determined the crystal structure of the Eg5 motor domain with ADP-Mg bound. This structure revealed a new intramolecular binding site of the neck-linker. In other kinesins, the neck-linker has been shown to be a critical mechanical element for force generation. The neck-linker of conventional kinesin is believed to undergo an ordered-to-disordered transition as it translocates along a microtubule. The structure of Eg5 showed an ordered neck-linker conformation in a position never observed previously. The docking of the neck-linker relies upon residues conserved only in the Eg5 subfamily of kinesin motors. Based on this new information, we suggest that the neck-linker of Eg5 may undergo an ordered-to-ordered transition during force production. This ratchet-like mechanism is consistent with the biological activity of Eg5.
Highlights
Prior to the separation of sister chromatids in anaphase, duplicated centrosomes are repositioned to opposite sides of the cell, forming the mitotic spindle as they move
Success of mitosis depends upon the coordinated and regulated activity of many cellular factors, including kinesin motor proteins, which are required for the assembly and function of the mitotic spindle
The refined Eg5 model revealed a protein with the general features expected of a kinesin motor, with six major -sheets sur
Summary
Prior to the separation of sister chromatids in anaphase, duplicated centrosomes are repositioned to opposite sides of the cell, forming the mitotic spindle as they move. We think it is more likely that the two structures may represent two different states that all kinesin motors assume at some point during force generation. This prediction is supported by the many different positions of this region observed in other kinesin motors [22,23,24,25,26].
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