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Tubulin polymerization promoting protein/p25 (TPPP/p25) modulates the dynamics and stability of the microtubule system and plays crucial role in the myelination of oligodendrocytes. Here we showed by CD, fluorescence, and NMR spectroscopies that Zn2+ is the first ligand that induces considerable rearrangement of the disordered TPPP/p25. Zinc finger motif (His2Cys2) (His61-Cys83) was identified within the flexible region of TPPP/p25 straddled by extended unstructured N- and C-terminal regions. The specific binding of the Zn2+ to TPPP/p25 induced the formation of molten globule but not that of a well-defined tertiary structure. The Zn2+-induced partially folded structure accommodating the zinc binding motif is localized at the single Trp76-containing region as demonstrated by fluorescence resonance energy transfer and quenching experiments. We showed that the Zn2+-induced change in the TPPP/p25 structure modified its interaction with tubulin and GTP coupled with functional consequences: the TPPP/p25-promote...

The disordered Tubulin Polymerization Promoting Protein/p25 (TPPP/p25) modulates the dynamics and stability of the microtubule system and plays a crucial role in differentiation of oligodendrocytes. Here we first demonstrated by multinuclear NMR that the extended disordered segments are localized at the N- and C-terminals straddling a flexible region. We showed by affinity chromatography, fluorescence spectroscopy and circular dichroism that GTP binds to TPPP/p25 likely within the flexible region; neither positions nor intensities of the peaks in the assigned terminals were affected by GTP. In addition, we demonstrated that TPPP/p25 specifically hydrolyses GTP in an Mg2+-dependent manner. The GTPase activity is comparable with the intrinsic activities of small G proteins suggesting its potential role in multiple physiological processes.