Multimodal microtubule binding by the Ndc80 kinetochore complex

Nat Struct Mol Biol. 2012 Nov;19(11):1161-7. doi: 10.1038/nsmb.2411. Epub 2012 Oct 21.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase B
  • Aurora Kinases
  • Calcium-Binding Proteins / metabolism
  • Cell Cycle Proteins / metabolism*
  • Cytoskeletal Proteins
  • Humans
  • M Phase Cell Cycle Checkpoints / physiology*
  • Microfilament Proteins / metabolism
  • Microscopy, Electron
  • Microtubules / metabolism*
  • Models, Biological*
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism
  • Tubulin / metabolism*

Substances

  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Microfilament Proteins
  • NDC80 protein, human
  • NUF2 protein, human
  • Nuclear Proteins
  • Tubulin
  • calponin
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases