The protein-binding N-terminal domain of human translation elongation factor 1Bβ possesses a dynamic α-helical structural organization.

Translation elongation factor 1Bβ (eEF1Bβ) is a metazoan-specific protein involved into the macromolecular eEF1B complex, containing also eEF1Bα and eEF1Bγ subunits. Both eEF1Bα and eEF1Bβ ensure the guanine nucleotide exchange on eEF1A while eEF1Bγ is thought to have a structural role. The structures of the eEF1Bβ catalytic C-terminal domain and neighboring central acidic region are known while the structure of the protein-binding N-terminal domain remains unidentified which prevents clear understanding of architecture of the eEF1B complex. Here we show that the N-terminal domain comprising initial 77 amino acids of eEF1Bβ, eEF1Bβ(1-77), is a monomer in solution with increased hydrodynamic volume. This domain binds eEF1Bγ in equimolar ratio. The CD spectra reveal that the secondary structure of eEF1Bβ(1-77) consists predominantly of α-helices and a portion of disordered region. Very rapid hydrogen/deuterium exchange for all eEF1Bβ(1-77) peptides favors a flexible tertiary organization of eEF1Bβ(1-77). Computational modeling of eEF1Bβ(1-77) suggests several conformation states each composed of three α-helices connected by flexible linkers. Altogether, the data imply that the protein-binding domain of eEF1Bβ shows flexible spatial organization which may be needed for interaction with eEF1Bγ or other protein partners.