Tubulin polymerization promoting proteins (TPPPs): Members of a new family with distinct structures and functions

Orsolya Vincze, Natália Tökési, J. Oláh, Emma Hlavanda, Ágnes Zotter, István Horváth, A. Lehotzky, L. Tirián, Katalin F. Medzihradszky, J. Kovács, F. Orosz, J. Ovádi

Research output: Contribution to journalArticle

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Abstract

TPPP/p25 is a brain-specific protein, which induces tubulin polymerization and microtubule (MT) bundling and is enriched in Lewy bodies characteristic of Parkinson's disease [Tirián et al. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 13976-13981]. We identified two human gene sequences, CG1-38 and p25β, which encoded homologous proteins, that we termed p20 and p18, respectively. These homologous proteins display 60% identity with tubulin polymerization promoting protein/p25 (TPPP/p25); however, the N-terminal segment of TPPP/p25 is missing. They could be clustered into three subfamilies present in mammals and other vertebrates. We cloned, isolated, and characterized the structural and functional properties of the recombinant human proteins at molecular, ultrastructural, and cellular levels using a number of tools. These data revealed that, while p20 behaved as a disorganized protein similarly to TPPP/p25, which was described as a flexible and inherently dynamic protein with a long unstructured N-terminal tail, p18 was featured in more ordered fashion. TPPP/p25 and p20 specifically attached to MTs causing MT bundling both in vitro and in vivo; p18 protein did not cross-link MTs, and it distributed homogeneously within the cytosol of the transfected HeLa cells. These data indicate that the two shorter homologues display distinct structural features that determine their associations to MTs. The properties of p20 resemble TPPP/p25. The bundling activity of these two proteins results in the stabilization of the microtubular network, which is likely related to their physiological functions.

Original languageEnglish
Pages (from-to)13818-13826
Number of pages9
JournalBiochemistry
Volume45
Issue number46
DOIs
Publication statusPublished - Nov 21 2006

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Tubulin
Polymerization
Proteins
Microtubules
Mammals
HeLa Cells
Recombinant Proteins
Cytosol
Parkinson Disease
Vertebrates
Tail
Brain
Stabilization
Genes

ASJC Scopus subject areas

  • Biochemistry

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Tubulin polymerization promoting proteins (TPPPs) : Members of a new family with distinct structures and functions. / Vincze, Orsolya; Tökési, Natália; Oláh, J.; Hlavanda, Emma; Zotter, Ágnes; Horváth, István; Lehotzky, A.; Tirián, L.; Medzihradszky, Katalin F.; Kovács, J.; Orosz, F.; Ovádi, J.

In: Biochemistry, Vol. 45, No. 46, 21.11.2006, p. 13818-13826.

Research output: Contribution to journalArticle

Vincze, Orsolya ; Tökési, Natália ; Oláh, J. ; Hlavanda, Emma ; Zotter, Ágnes ; Horváth, István ; Lehotzky, A. ; Tirián, L. ; Medzihradszky, Katalin F. ; Kovács, J. ; Orosz, F. ; Ovádi, J. / Tubulin polymerization promoting proteins (TPPPs) : Members of a new family with distinct structures and functions. In: Biochemistry. 2006 ; Vol. 45, No. 46. pp. 13818-13826.
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AU - Vincze, Orsolya

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AU - Hlavanda, Emma

AU - Zotter, Ágnes

AU - Horváth, István

AU - Lehotzky, A.

AU - Tirián, L.

AU - Medzihradszky, Katalin F.

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AU - Orosz, F.

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