Evolutionarily conserved binding of translationally controlled tumor protein to eukaryotic elongation factor 1B.

ABSTRACT: Translationally controlled tumor protein (TCTP) is an abundant protein that is highly conserved in eukaryotes. However, its primary function is still not clear. Human TCTP interacts with the metazoan-specific eukaryotic elongation factor 1B? (eEF1B?) and inhibits its guanine nucleotide exchange factor (GEF) activity, but the structural mechanism remains unknown. The interaction between TCTP and eEF1B? 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 eEF1B? is not responsible for binding to TCTP but rather a previously unnoticed central acidic region (CAR) domain in eEF1B?. The mutagenesis data and the structural model of the TCTP-eEF1B? CAR domain complex revealed the key binding residues. These residues are highly conserved in eukaryotic TCTPs and in eEF1B GEFs, including the eukaryotically conserved eEF1B?, implying the interaction may be conserved in all eukaryotes. Interactions were confirmed between TCTP and the eEF1B? CAR domain for human, fission yeast, and unicellular photosynthetic microalgal proteins, suggesting that involvement in protein translation through the conserved interaction with eEF1B represents a primary function of TCTP.

SUBMITTER: Wu H 

PROVIDER: S-EPMC4423661 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature