The C-terminal domain of TPX2 is made of alpha-helical tandem repeats. (December 2016)

• Record Type: Journal Article
• Authors: Sanchez-Pulido, Luis; Perez, Laurent; Kuhn, Steffen; Vernos, Isabelle; Andrade-Navarro, Miguel
• Is Part Of: BMC structural biology. Volume 16:Number 1(2016)
• Page Start: 1
• Page End: 8
• Publication Date: 2016-12
• Subjects: TPX2 -- Protein sequence tandem repeats -- Protein sequence analysis -- Protein structure prediction -- Alpha-solenoid -- Circular Dichroism; Molecular biology -- Periodicals; Macromolecular Systems -- Periodicals; Models, Structural -- Periodicals; 572.33
• DOI: 10.1186/s12900-016-0070-8
• Languages: English
• ISSNs: 1472-6807

Abstract

Abstract Background 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. Methods We have used computational sequence analyses and structural predictions of proteins of the TPX2 family, supported with Circular Dichroism (CD) measurements. Results 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 inDrosophila ). Conclusions 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.