title: Crystal structure of the C-terminal domain of the ɛ subunit of human translation initiation factor eIF2B.
abstract: Eukaryotic translation initiation factor eIF2B, the guanine nucleotide exchange factor (GEF) for eIF2, catalyzes conversion of eIF2·GDP to eIF2·GTP. The eIF2B is composed of five subunits, α, β, γ, δ and ɛ, within which the ɛ subunit is responsible for catalyzing the guanine exchange reaction. Here we present the crystal structure of the C-terminal domain of human eIF2Bɛ (eIF2Bɛ-CTD) at 2.0-Å resolution. The structure resembles a HEAT motif and three charge-rich areas on its surface can be identified. When compared to yeast eIF2Bɛ-CTD, one area involves highly conserved AA boxes while the other two are only partially conserved. In addition, the previously reported mutations in human eIF2Bɛ-CTD, which are related to the loss of the GEF activity and human VWM disease, have been discussed. Based on the structure, most of such mutations tend to destabilize the HEAT motif.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wei
authors.forename: Minze
authors.initials: M
authors.lastname: Jia
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Hang
authors.initials: H
authors.lastname: Xu
authors.forename: Weimin
authors.initials: W
authors.lastname: Gong
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D020717:Eukaryotic Initiation Factor-2B / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000096:biosynthesis / Q000737:chemistry; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000737:chemistry; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D013499:Surface Properties
chemical_list: D020717:Eukaryotic Initiation Factor-2B; D021122:Protein Subunits; D011994:Recombinant Proteins