Structural highlights
Function
[EF1D_HUMAN] Isoform 1: EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP, regenerating EF-1-alpha for another round of transfer of aminoacyl-tRNAs to the ribosome. Isoform 2: Regulates induction of heat-shock-responsive genes through association with heat shock transcription factors and direct DNA-binding at heat shock promoter elements (HSE).
Publication Abstract from PubMed
Translationally-controlled tumor protein (TCTP) is an abundant protein which is highly conserved in eukaryotes. However, its primary function is still not clear. Human TCTP interacts with the metazoan-specific eukaryotic elongation factor 1Bdelta (eEF1Bdelta) and inhibits its guanine nucleotide exchange factor (GEF) activity, but the structural mechanism remains unknown. The interaction between TCTP and eEF1Bdelta was investigated by NMR titration, structure determination, paramagnetic relaxation enhancement, site-directed mutagenesis, isothermal titration calorimetry, and HADDOCK docking. We first demonstrated that the catalytic GEF domain of eEF1Bdelta is not responsible for binding to TCTP, but rather a previously unnoticed central acidic region (CAR) domain in eEF1Bdelta. The mutagenesis data and the structural model of the TCTP-eEF1Bdelta CAR domain complex revealed the key binding residues. These residues are highly conserved in eukaryotic TCTPs and in eEF1B GEFs including the eukaryotically-conserved eEF1Balpha, implying the interaction may be conserved in all eukaryotes. Interactions were confirmed between TCTP and the eEF1Balpha CAR domain for human, fission yeast and unicellular photosynthetic microalga proteins, suggesting that involvement in protein translation through the conserved interaction with eEF1B represents a primary function of TCTP.
Evolutionarily Conserved Binding of Translationally-Controlled Tumor Protein to Eukaryotic Elongation Factor 1B.,Wu H, Gong W, Yao X, Wang J, Perrett S, Feng Y J Biol Chem. 2015 Jan 29. pii: jbc.M114.628594. PMID:25635048[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wu H, Gong W, Yao X, Wang J, Perrett S, Feng Y. Evolutionarily Conserved Binding of Translationally-Controlled Tumor Protein to Eukaryotic Elongation Factor 1B. J Biol Chem. 2015 Jan 29. pii: jbc.M114.628594. PMID:25635048 doi:http://dx.doi.org/10.1074/jbc.M114.628594
