XTACC3-XMAP215 association reveals an asymmetric interaction promoting microtubule elongation

Nat Commun. 2014 Sep 29:5:5072. doi: 10.1038/ncomms6072.

Abstract

chTOG is a conserved microtubule polymerase that catalyses the addition of tubulin dimers to promote microtubule growth. chTOG interacts with TACC3, a member of the transforming acidic coiled-coil (TACC) family. Here we analyse their association using the Xenopus homologues, XTACC3 (TACC3) and XMAP215 (chTOG), dissecting the mechanism by which their interaction promotes microtubule elongation during spindle assembly. Using SAXS, we show that the TACC domain (TD) is an elongated structure that mediates the interaction with the C terminus of XMAP215. Our data suggest that one TD and two XMAP215 molecules associate to form a four-helix coiled-coil complex. A hybrid methods approach was used to define the precise regions of the TACC heptad repeat and the XMAP215 C terminus required for assembly and functioning of the complex. We show that XTACC3 can induce the recruitment of larger amounts of XMAP215 by increasing its local concentration, thereby promoting efficient microtubule elongation during mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calorimetry
  • Circular Dichroism
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Spectroscopy
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Protein Structure, Tertiary
  • Scattering, Small Angle
  • Spindle Apparatus / metabolism
  • Surface Plasmon Resonance
  • Temperature
  • Transcription Factors / metabolism*
  • Xenopus
  • Xenopus Proteins / metabolism*

Substances

  • CKAP5 protein, Xenopus
  • Microtubule-Associated Proteins
  • TACC3 protein, Xenopus
  • Transcription Factors
  • Xenopus Proteins