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.
MeSH Terms
Amino Acid Sequence
Chromosomal Proteins, Non-Histone/chemistry,metabolism
Humans
Kinetochores/chemistry,metabolism
Macromolecular Substances/chemistry,metabolism
Microscopy, Electron
Microtubules/chemistry,metabolism
Mitosis/physiology
Models, Molecular
Molecular Sequence Data
Nuclear Proteins/chemistry,metabolism,ultrastructure
Protein Conformation
Saccharomyces cerevisiae/metabolism
Saccharomyces cerevisiae Proteins/chemistry,metabolism,ultrastructure
Sequence Alignment
Stress, Mechanical
Chemicals
Chromosomal Proteins, Non-Histone
Macromolecular Substances
NDC80 protein, S cerevisiae
Nuclear Proteins
Saccharomyces cerevisiae Proteins
Spc24 protein, S cerevisiae
Spc25 protein, S cerevisiae
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wang Hong-Wei
Life Science Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA.
Long Sydney
Ciferri Claudio
Westermann Stefan
Drubin David
Barnes Georjana
Nogales Eva
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