Abstract
BackgroundTPX2 (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.MethodsWe have used computational sequence analyses and structural predictions of proteins of the TPX2 family, supported with Circular Dichroism (CD) measurements.ResultsHere, 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).ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12900-016-0070-8) contains supplementary material, which is available to authorized users.
Highlights
TPX2 (Targeting Protein for Xklp2) is essential for spindle assembly, activation of the mitotic kinase Aurora A and for triggering microtubule nucleation
TPX2 was initially identified as a Microtubule-Associated Protein (MAP) responsible for the localization of the kinesin-like protein Xklp2 to microtubule minus ends during mitosis [3, 4]
It accumulates in the nucleus during S/G2, at the spindle poles during mitosis, and it is degraded in early G1
Summary
TPX2 (Targeting Protein for Xklp2) is essential for spindle assembly, activation of the mitotic kinase Aurora A and for triggering microtubule nucleation. Spindle assembly involves the activities of multiple proteins that participate in localized microtubule nucleation, dynamics, and organization [1]. One of these proteins is TPX2 [2]. Experiments in Xenopus egg extracts have shown that TPX2 is regulated by the GTP-bound form of Ran [6] and triggers the local nucleation of TPX2 has other important functions, including a role in spindle pole organization [8] and in targeting and activating the mitotic kinase Aurora A [9,10,11,12]. Little is known about the structure of TPX2 proteins
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