title: Structural comparison of the Caenorhabditis elegans and human Ndc80 complexes bound to microtubules reveals distinct binding behavior.
abstract: During cell division, kinetochores must remain tethered to the plus ends of dynamic microtubule polymers. However, the molecular basis for robust kinetochore-microtubule interactions remains poorly understood. The conserved four-subunit Ndc80 complex plays an essential and direct role in generating dynamic kinetochore-microtubule attachments. Here we compare the binding of theCaenorhabditis elegansand human Ndc80 complexes to microtubules at high resolution using cryo-electron microscopy reconstructions. Despite the conserved roles of the Ndc80 complex in diverse organisms, we find that the attachment mode of these complexes for microtubules is distinct. The human Ndc80 complex binds every tubulin monomer along the microtubule protofilament, whereas theC. elegansNdc80 complex binds more tightly to β-tubulin. In addition, theC. elegansNdc80 complex tilts more toward the adjacent protofilament. These structural differences in the Ndc80 complex between different species may play significant roles in the nature of kinetochore-microtubule interactions.
authors.affiliation: Laboratory of Structure Cell Biology, Department of Integrative Structure and Computational Biology, Scripps Research Institute, La Jolla, CA 92037 kubalek@scripps.edu.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Wilson-Kubalek
authors.affiliation: Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.
authors.forename: Iain M
authors.initials: IM
authors.lastname: Cheeseman
authors.affiliation: Laboratory of Structure Cell Biology, Department of Integrative Structure and Computational Biology, Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Milligan
mesh_terms: D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000378:metabolism*; D020285:Cryoelectron Microscopy; D003598:Cytoskeletal Proteins; D018386:Kinetochores / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D014404:Tubulin / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; C492665:NDC-80 protein, C elegans; C120529:NDC80 protein, human; D009687:Nuclear Proteins; D014404:Tubulin