fig2

Figure 2. The peculiar structure of TCTP. (A) A cartoon representation of the secondary structure of human TCTP. Reference sequence from UniProt P13693^[11]. β-strands, α-helices and turns elements are indicated in the legend. The N-terminal region includes a flexible loop extending from β5 to β6 strands. It contains a highly conserved signature and the Ser46 and Ser64 residues which are phosphorylated by the polo-like kinase Plk1, a crucial player in mitosis. A second conserved signature is found in the C-terminal region; (B) The crystal structure of the human TCTP (PDB Code 1YZ1^[12]) discloses the α-helical hairpin (formed by Helix H2 and Helix H3), whose structure is similar to the H5-H6 helices of BCL-2 family proteins, and the β-stranded domain that shows a structural analogy with the guanine nucleotide exchange factors (GEF) Mss4/Dss4 protein families^[13], suggesting a similar role for TCTP as GEF for Ras homolog enriched in brain (Rheb) in the mTORC1 pathway^[14]. The flexible loop is not detectable in the crystal structure. TCTP: Translationally controlled tumor protein.