Quaternary organization of the human eEF1B complex reveals unique multi-GEF domain assembly

Protein synthesis in eukaryotic cell is spatially and structurally compartmentalized that ensures high efficiency of this process. One of the distinctive features of higher eukaryotes is the existence of stable multi-protein complexes of aminoacyl-tRNA synthetases and translation elongation factors. Here, we report a quaternary organization of the human guanine-nucleotide exchange factor (GEF) complex, eEF1B, comprising alpha, beta and gamma subunits that specifically associate into a heterotrimeric form eEF1B(alpha beta gamma)(3). As both the eEF1B alpha and eEF1B beta proteins have structurally conserved GEF domains, their total number within the complex is equal to six. Such, so far, unique structural assembly of the guanine-nucleotide exchange factors within a stable complex may be considered as a 'GEF hub' that ensures efficient maintenance of the translationally active GTP-bound conformation of eEF1A in higher eukaryotes.

Automated summary

Protein synthesis in eukaryotic cells is compartmentalized, ensuring high efficiency. Higher eukaryotes have stable multi-protein complexes of aminoacyl-tRNA synthetases and translation elongation factors. The human guanine-nucleotide exchange factor (GEF) complex eEF1B is organized in a quaternary structure, with alpha, beta, and gamma subunits forming a heterotrimeric form eEF1B(alpha beta gamma)(3). This unique assembly of GEFs within a stable complex serves as a "GEF hub" that maintains the translationally active GTP-bound conformation of eEF1A in higher eukaryotes.