title: KIF14 binds tightly to microtubules and adopts a rigor-like conformation.
abstract: The mitotic kinesin motor protein KIF14 is essential for cytokinesis during cell division and has been implicated in cerebral development and a variety of human cancers. Here we show that the mouse KIF14 motor domain binds tightly to microtubules and does not display typical nucleotide-dependent changes in this affinity. It also has robust ATPase activity but very slow motility. A crystal structure of the ADP-bound form of the KIF14 motor domain reveals a dramatically opened ATP-binding pocket, as if ready to exchange its bound ADP for Mg·ATP. In this state, the central β-sheet is twisted ~10° beyond the maximal amount observed in other kinesins. This configuration has only been seen in the nucleotide-free states of myosins-known as the "rigor-like" state. Fitting of this atomic model to electron density maps from cryo-electron microscopy indicates a distinct binding configuration of the motor domain to microtubules. We postulate that these properties of KIF14 are well suited for stabilizing midbody microtubules during cytokinesis.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, 18 Stuart St., Rm. 652, Kingston, ON K7L 3 N6, Canada.
authors.forename: Kritica
authors.initials: K
authors.lastname: Arora
authors.affiliation: Institute for Research in Immunology and Cancer, Département de Médecine, Université de Montréal, P.O. Box 6128, Station Centre-Ville, Montréal, QC H3C 3 J7, Canada.
authors.forename: Lama
authors.initials: L
authors.lastname: Talje
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Asenjo
authors.affiliation: Institute for Research in Immunology and Cancer, Département de Médecine, Université de Montréal, P.O. Box 6128, Station Centre-Ville, Montréal, QC H3C 3 J7, Canada.
authors.forename: Parker
authors.initials: P
authors.lastname: Andersen
authors.affiliation: Institute for Research in Immunology and Cancer, Département de Médecine, Université de Montréal, P.O. Box 6128, Station Centre-Ville, Montréal, QC H3C 3 J7, Canada.
authors.forename: Kaleem
authors.initials: K
authors.lastname: Atchia
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, 18 Stuart St., Rm. 652, Kingston, ON K7L 3 N6, Canada.
authors.forename: Monika
authors.initials: M
authors.lastname: Joshi
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Hernando
authors.initials: H
authors.lastname: Sosa
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, 18 Stuart St., Rm. 652, Kingston, ON K7L 3 N6, Canada. Electronic address: allinghj@queensu.ca.
authors.forename: John S
authors.initials: JS
authors.lastname: Allingham
authors.affiliation: Institute for Research in Immunology and Cancer, Département de Médecine, Université de Montréal, P.O. Box 6128, Station Centre-Ville, Montréal, QC H3C 3 J7, Canada. Electronic address: benjamin.kwok@umontreal.ca.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Kwok
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D000251:Adenosine Triphosphatases / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D016547:Kinesins / Q000737:chemistry*; D007700:Kinetics; D051379:Mice; D008870:Microtubules / Q000737:chemistry* / Q000648:ultrastructure; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary
chemical_list: D000244:Adenosine Diphosphate; D000251:Adenosine Triphosphatases; C581966:Kif14 protein, mouse; D016547:Kinesins
keywords: KIF14; crystal structure; kinesin; microtubules; motor protein