title: Looping in on Ndc80 - how does a protein loop at the kinetochore control chromosome segregation?
abstract: Segregation of chromosomes during mitosis requires the interaction of dynamic microtubules with the kinetochore, a large protein structure established on the centromere region of sister chromatids. The core microtubule-binding activity of the kinetochore resides in the KMN network, an outer kinetochore complex. As part of the KMN network, the Ndc80 complex, which is composed of Ndc80, Nuf2, Spc24, and Spc25, is able to bind directly to microtubules and has the ability to track with depolymerizing microtubules to produce chromosome movement. The Ndc80 complex binds directly to microtubules through a calponin homology domain and an unstructured tail in the N terminus of the Ndc80 protein. A recent flurry of papers has highlighted the importance of an internal loop region in Ndc80 in establishing end-on attachment to microtubules. Here I discuss these recent findings that suggest that the Ndc80 internal loop functions as a binding site for proteins required for kinetochore-microtubule interactions.
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark. jakob.nilsson@cpr.ku.dk
authors.forename: Jakob
authors.initials: J
authors.lastname: Nilsson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism; D020090:Chromosome Segregation; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000737:chemistry / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D014714:Vertebrates
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C116003:DAM1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D008869:Microtubule-Associated Proteins; C112472:NDC80 protein, S cerevisiae; C120529:NDC80 protein, human; C087340:NUF2 protein, S cerevisiae; D009687:Nuclear Proteins; C484695:SPC24 protein, human; C484694:SPC25 protein, human; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C499592:TAH11 protein, S cerevisiae; C094879:dis1 protein, S pombe