XTACC3–XMAP215 association reveals an asymmetric interaction promoting microtubule elongation

• Published in: Nature communications 2014-09, Vol.5 (1), p.5072-5072, Article 5072
• Main Authors: Mortuza, Gulnahar B., Cavazza, Tommaso, Garcia-Mayoral, Maria Flor, Hermida, Dario, Peset, Isabel, Pedrero, Juan G., Merino, Nekane, Blanco, Francisco J., Lyngsø, Jeppe, Bruix, Marta, Pedersen, Jan Skov, Vernos, Isabelle, Montoya, Guillermo
• Format: Article
• Language: English
• Subjects: 101/6; 631/45/535; 631/45/612; 631/80/128/1653; 82/1; 82/83; Amino Acid Sequence; Animals; Calorimetry; Circular Dichroism; Humanities and Social Sciences; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Microtubule-Associated Proteins - metabolism; Microtubules - metabolism; Molecular Sequence Data; multidisciplinary; Mutation; Protein Structure, Tertiary; Scattering, Small Angle; Science; Science (multidisciplinary); Spindle Apparatus - metabolism; Surface Plasmon Resonance; Temperature; Transcription Factors - metabolism; Xenopus; Xenopus Proteins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms6072

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. chTOG, a microtubule polymerase, interacts with TACC3 during mitosis to regulate spindle formation. By studying their Xenopus homologues, Mortuza et al . discover that one TACC3 recruits two chTOG molecules to the spindle, increasing its local concentration and promoting microtubule elongation.