title: Solution structure of human initiation factor eIF2alpha reveals homology to the elongation factor eEF1B.
abstract: The GTP-bound form of the trimeric eukaryotic translation initiation factor 2 (eIF2) transfers aminoacylated initiator methionyl tRNA onto the 40S ribosome. We have solved with solution NMR the structure of the alpha subunit of human eIF2 (heIF2alpha). The protein consists of two domains that are mobile relative to each other. The N-terminal domain has an S1-type oligonucleotide/oligosaccharide binding-fold subdomain and an alpha-helical subdomain. The C-terminal domain adopts an alphabeta-fold very similar to the C-terminal domain of elongation factor (eEF) 1Balpha, the guanine-nucleotide exchange factor for eEF1A. The structural and functional similarities found between eIF2alpha/eIF2gamma and eEF1Balpha/eEF1A suggest a model for the interaction of eIF2alpha with eIF2gamma, and eIF2 with Met-tRNAiMet. It further indicates a previously unrecognized evolutionary lineage of eIF2alpha/gamma from the functionally related elongation factor eEF1Balpha/eEF1A complex.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Ito
authors.forename: Assen
authors.initials: A
authors.lastname: Marintchev
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015852:Eukaryotic Initiation Factor-2 / Q000737:chemistry* / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D020648:Peptide Elongation Factor 1 / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry*; D016415:Sequence Alignment
chemical_list: D015852:Eukaryotic Initiation Factor-2; D020648:Peptide Elongation Factor 1; D021122:Protein Subunits