title: Tubulin polymerization promoting proteins (TPPPs): members of a new family with distinct structures and functions.
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 p25beta, 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.
authors.affiliation: Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, H-1113, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Vincze
authors.forename: Natália
authors.initials: N
authors.lastname: Tökési
authors.forename: Judit
authors.initials: J
authors.lastname: Oláh
authors.forename: Emma
authors.initials: E
authors.lastname: Hlavanda
authors.forename: Agnes
authors.initials: A
authors.lastname: Zotter
authors.forename: István
authors.initials: I
authors.lastname: Horváth
authors.forename: Attila
authors.initials: A
authors.lastname: Lehotzky
authors.forename: Laszló
authors.initials: L
authors.lastname: Tirián
authors.forename: Katalin F
authors.initials: KF
authors.lastname: Medzihradszky
authors.forename: János
authors.initials: J
authors.lastname: Kovács
authors.forename: Ferenc
authors.initials: F
authors.lastname: Orosz
authors.forename: Judit
authors.initials: J
authors.lastname: Ovádi
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002942:Circular Dichroism; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D010802:Phylogeny; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance
chemical_list: D017931:DNA Primers; D009419:Nerve Tissue Proteins; C118136:TPPP protein, human