title: The C-terminal domain of TPX2 is made of alpha-helical tandem repeats.
abstract: TPX2 (Targeting Protein for Xklp2) is essential for spindle assembly, activation of the mitotic kinase Aurora A and for triggering microtubule nucleation. Homologs of TPX2 in Chordata and plants were previously identified. Currently, proteins of the TPX2 family have little structural information and only small parts are covered by defined protein domains.
  
  
  
  We have used computational sequence analyses and structural predictions of proteins of the TPX2 family, supported with Circular Dichroism (CD) measurements.
  
  
  
  Here, we report our finding that the C-terminal domain of TPX2, which is responsible of its microtubule nucleation capacity and is conserved in all members of the family, is actually formed by tandem repeats, covering well above 2/3 of the protein. We propose that this region forms a flexible solenoid involved in protein-protein interactions. Structural prediction and molecular modeling, combined with Circular Dichroism (CD) measurements reveal a predominant alpha-helical content. Furthermore, we identify full length homologs in fungi and shorter homologs with a different domain organization in diptera (including a paralogous expansion in Drosophila).
  
  
  
  Our results, represent the first computational and biophysical analysis of the TPX2 proteins family and help understand the structure and evolution of this conserved protein family to direct future structural studies.
authors: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
authors: Luis
authors: L
authors: Sanchez-Pulido
authors: Center for Genomic Regulation, C/ Dr Aiguader 88, 08003, Barcelona, Spain.|Institute for Research in Biomedicine, Università della Svizzera italiana, Via Vincenzo Vela 6, CH-6500, Bellinzona, Switzerland.
authors: Laurent
authors: L
authors: Perez
authors: Faculty of Biology, Johannes-Gutenberg University, Gresemundweg 2, 55128, Mainz, Germany.
authors: Steffen
authors: S
authors: Kuhn
authors: Center for Genomic Regulation, C/ Dr Aiguader 88, 08003, Barcelona, Spain.
authors: Isabelle
authors: I
authors: Vernos
authors: Faculty of Biology, Johannes-Gutenberg University, Gresemundweg 2, 55128, Mainz, Germany. Andrade@uni-mainz.de.|Institute of Molecular Biology, Ackermannweg 4, 55128, Mainz, Germany. Andrade@uni-mainz.de.
authors: Miguel A
authors: MA
authors: Andrade-Navarro
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002942:Circular Dichroism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D016415:Sequence Alignment; D014981:Xenopus / Q000378:metabolism; D029867:Xenopus Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D029681:Arabidopsis Proteins; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; C535123:TPX2 protein, Arabidopsis; C486551:TPX2 protein, Xenopus; D029867:Xenopus Proteins
keywords: Alpha-solenoid; Circular Dichroism; Protein sequence analysis; Protein sequence tandem repeats; Protein structure prediction; TPX2