title: Structural basis for microtubule recognition by the human kinetochore Ska complex.
abstract: The ability of kinetochores (KTs) to maintain stable attachments to dynamic microtubule structures ('straight' during microtubule polymerization and 'curved' during microtubule depolymerization) is an essential requirement for accurate chromosome segregation. Here we show that the kinetochore-associated Ska complex interacts with tubulin monomers via the carboxy-terminal winged-helix domain of Ska1, providing the structural basis for the ability to bind both straight and curved microtubule structures. This contrasts with the Ndc80 complex, which binds straight microtubules by recognizing the dimeric interface of tubulin. The Ska1 microtubule-binding domain interacts with tubulins using multiple contact sites that allow the Ska complex to bind microtubules in multiple modes. Disrupting either the flexibility or the tubulin contact sites of the Ska1 microtubule-binding domain perturbs normal mitotic progression, explaining the critical role of the Ska complex in maintaining a firm grip on dynamic microtubules.
authors.affiliation: 1] Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, EH9 3JR Edinburgh, UK [2].
authors.forename: Maria Alba
authors.initials: MA
authors.lastname: Abad
authors.affiliation: 1] Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, EH9 3JR Edinburgh, UK [2].
authors.forename: Bethan
authors.initials: B
authors.lastname: Medina
authors.affiliation: 1] Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland [2].
authors.forename: Anna
authors.initials: A
authors.lastname: Santamaria
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, EH9 3JR Edinburgh, UK.
authors.forename: Juan
authors.initials: J
authors.lastname: Zou
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, EH9 3JR Edinburgh, UK.
authors.forename: Carla
authors.initials: C
authors.lastname: Plasberg-Hill
authors.affiliation: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Arumugam
authors.initials: A
authors.lastname: Madhumalar
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, EH9 3JR Edinburgh, UK.
authors.forename: Uma
authors.initials: U
authors.lastname: Jayachandran
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors.forename: Patrick Marc
authors.initials: PM
authors.lastname: Redli
authors.affiliation: 1] Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, EH9 3JR Edinburgh, UK [2] Department of Biotechnology, Technische Universität Berlin, 13353 Berlin, Germany.
authors.forename: Juri
authors.initials: J
authors.lastname: Rappsilber
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, EH9 3JR Edinburgh, UK.
authors.forename: A Arockia
authors.initials: AA
authors.lastname: Jeyaprakash
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D020090:Chromosome Segregation; D003598:Cytoskeletal Proteins; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009687:Nuclear Proteins; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; C120529:NDC80 protein, human; D009687:Nuclear Proteins; C516427:SKA1 protein, human; D014404:Tubulin; C000602228:ska-1 protein, C elegans