title: Multimodal microtubule binding by the Ndc80 kinetochore complex.
abstract: The Ndc80 complex is a key site of kinetochore-microtubule attachment during cell division. The human complex engages microtubules with a globular 'head' formed by tandem calponin-homology domains and an 80-amino-acid unstructured 'tail' that contains sites of phosphoregulation by the Aurora B kinase. Using biochemical, cell biological and electron microscopy analyses, we dissected the roles of the tail in binding of microtubules and mediation of cooperative interactions between Ndc80 complexes. Two segments of the tail that contain Aurora B phosphorylation sites become ordered at interfaces; one with tubulin and the second with an adjacent Ndc80 head on the microtubule surface, forming interactions that are disrupted by phosphorylation. We propose a model in which Ndc80's interaction with either growing or shrinking microtubule ends can be tuned by the phosphorylation state of its tail.
authors.affiliation: Biophysics Graduate Group, University of California Berkeley, Berkeley, California, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Alushin
authors.forename: Vivek
authors.initials: V
authors.lastname: Musinipally
authors.forename: Daniel
authors.initials: D
authors.lastname: Matson
authors.forename: John
authors.initials: J
authors.lastname: Tooley
authors.forename: P Todd
authors.initials: PT
authors.lastname: Stukenberg
authors.forename: Eva
authors.initials: E
authors.lastname: Nogales
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*; D000096985:Calponins
chemical_list: D064107:Aurora Kinase B; D064127:Aurora Kinases; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D014404:Tubulin; D000096985:Calponins; C120529:NDC80 protein, human; C490197:NUF2 protein, human; C576921:AURKB protein, human