title: XTACC3-XMAP215 association reveals an asymmetric interaction promoting microtubule elongation.
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.
authors.affiliation: 1] Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Macromolecular Crystallography Group, c/Melchor Fdez. Almagro 3, 28029 Madrid, Spain [2] Macromolecular Crystallography Group, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
authors.forename: Gulnahar B
authors.initials: GB
authors.lastname: Mortuza
authors.affiliation: 1] Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain [2] Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cavazza
authors.affiliation: Department of Biological Physical Chemistry, Spanish National Research Council (CSIC), Institute of Physical Chemistry 'Rocasolano', Serrano 119, 28006 Madrid, Spain.
authors.forename: Maria Flor
authors.initials: MF
authors.lastname: Garcia-Mayoral
authors.affiliation: 1] Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Macromolecular Crystallography Group, c/Melchor Fdez. Almagro 3, 28029 Madrid, Spain [2] Macromolecular Crystallography Group, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
authors.forename: Dario
authors.initials: D
authors.lastname: Hermida
authors.affiliation: 1] Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain [2] Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Peset
authors.affiliation: Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Macromolecular Crystallography Group, c/Melchor Fdez. Almagro 3, 28029 Madrid, Spain.
authors.forename: Juan G
authors.initials: JG
authors.lastname: Pedrero
authors.affiliation: Structural Biology Unit, CIC bioGUNE, 48160 Derio, Spain.
authors.forename: Nekane
authors.initials: N
authors.lastname: Merino
authors.affiliation: 1] Structural Biology Unit, CIC bioGUNE, 48160 Derio, Spain [2] IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry Aarhus University, Gustav Wieds Vej 14, Building 1590-252, 8000 Aarhus C, Denmark.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Lyngsø
authors.affiliation: Department of Biological Physical Chemistry, Spanish National Research Council (CSIC), Institute of Physical Chemistry 'Rocasolano', Serrano 119, 28006 Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Bruix
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry Aarhus University, Gustav Wieds Vej 14, Building 1590-252, 8000 Aarhus C, Denmark.
authors.forename: Jan Skov
authors.initials: JS
authors.lastname: Pedersen
authors.affiliation: 1] Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain [2] Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain [3] Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, 08010 Barcelona, Spain.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vernos
authors.affiliation: 1] Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Macromolecular Crystallography Group, c/Melchor Fdez. Almagro 3, 28029 Madrid, Spain [2] Macromolecular Crystallography Group, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Montoya
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002151:Calorimetry; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D008941:Spindle Apparatus / Q000378:metabolism; D020349:Surface Plasmon Resonance; D013696:Temperature; D014157:Transcription Factors / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: C486738:CKAP5 protein, Xenopus; D008869:Microtubule-Associated Proteins; C474872:TACC3 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins