title: Architecture and flexibility of the yeast Ndc80 kinetochore complex.
abstract: Kinetochores mediate microtubule-chromosome attachment and ensure accurate segregation of sister chromatids. The highly conserved Ndc80 kinetochore complex makes direct contacts with the microtubule and is essential for spindle checkpoint signaling. It contains a long coiled-coil region with globular domains at each end involved in kinetochore localization and microtubule binding, respectively. We have directly visualized the architecture of the yeast Ndc80 complex and found a dramatic kink within the 560-A coiled-coil rod located about 160 A from the larger globular head. Comparison of our electron microscopy images to the structure of the human Ndc80 complex allowed us to position the kink proximal to the microtubule-binding end and to define the conformational range of the complex. The position of the kink coincides with a coiled-coil breaking region conserved across eukaryotes. We hypothesize that the kink in Ndc80 is essential for correct kinetochore geometry and could be part of a tension-sensing mechanism at the kinetochore.
authors.affiliation: Life Science Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Sydney
authors.initials: S
authors.lastname: Long
authors.forename: Claudio
authors.initials: C
authors.lastname: Ciferri
authors.forename: Stefan
authors.initials: S
authors.lastname: Westermann
authors.forename: David
authors.initials: D
authors.lastname: Drubin
authors.forename: Georjana
authors.initials: G
authors.lastname: Barnes
authors.forename: Eva
authors.initials: E
authors.lastname: Nogales
mesh_terms: D000595:Amino Acid Sequence; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000737:chemistry / Q000378:metabolism; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D008854:Microscopy, Electron; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D016415:Sequence Alignment; D013314:Stress, Mechanical
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D046911:Macromolecular Substances; C112472:NDC80 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C500717:Spc24 protein, S cerevisiae; C500718:Spc25 protein, S cerevisiae
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