title: The family-specific α4-helix of the kinesin-13, MCAK, is critical to microtubule end recognition.
abstract: Kinesins that influence the dynamics of microtubule growth and shrinkage require the ability to distinguish between the microtubule end and the microtubule lattice. The microtubule depolymerizing kinesin MCAK has been shown to specifically recognize the microtubule end. This ability is key to the action of MCAK in regulating microtubule dynamics. We show that the α4-helix of the motor domain is crucial to microtubule end recognition. Mutation of the residues K524, E525 and R528, which are located in the C-terminal half of the α4-helix, specifically disrupts the ability of MCAK to recognize the microtubule end. Mutation of these residues, which are conserved in the kinesin-13 family and discriminate members of this family from translocating kinesins, impairs the ability of MCAK to discriminate between the microtubule lattice and the microtubule end.
authors.affiliation: School of Life Sciences, University of Nottingham, Medical School, QMC, Nottingham NG7 2UH, UK.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Patel
authors.affiliation: School of Life Sciences, University of Nottingham, Medical School, QMC, Nottingham NG7 2UH, UK.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Belsham
authors.affiliation: School of Life Sciences, University of Nottingham, Medical School, QMC, Nottingham NG7 2UH, UK.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Rathbone
authors.affiliation: School of Life Sciences, University of Nottingham, Medical School, QMC, Nottingham NG7 2UH, UK.
authors.forename: Bill
authors.initials: B
authors.lastname: Wickstead
authors.affiliation: School of Life Sciences, University of Nottingham, Medical School, QMC, Nottingham NG7 2UH, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gell
authors.affiliation: School of Life Sciences, University of Nottingham, Medical School, QMC, Nottingham NG7 2UH, UK claire.friel@nottingham.ac.uk.
authors.forename: Claire T
authors.identifier: 0000-0001-8395-5301
authors.initials: CT
authors.lastname: Friel
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D006801:Humans; D016547:Kinesins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: C091489:KIF2C protein, human; D016547:Kinesins
keywords: ATP turnover; MCAK; depolymerization; kinesin-13; microtubule; microtubule end recognition