title: Crystal structure of the mitotic spindle kinesin Eg5 reveals a novel conformation of the neck-linker.
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.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143, USA. turner@msg.ucsf.edu
authors.forename: J
authors.initials: J
authors.lastname: Turner
authors.forename: R
authors.initials: R
authors.lastname: Anderson
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: C
authors.initials: C
authors.lastname: Beraud
authors.forename: R
authors.initials: R
authors.lastname: Fletterick
authors.forename: R
authors.initials: R
authors.lastname: Sakowicz
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D016547:Kinesins / Q000737:chemistry* / Q000235:genetics; D008938:Mitosis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010920:Placenta / Q000737:chemistry; D011487:Protein Conformation; D029867:Xenopus Proteins
chemical_list: C088335:KIF11 protein, Xenopus; D029867:Xenopus Proteins; D000244:Adenosine Diphosphate; D016547:Kinesins