title: The eIF1A solution structure reveals a large RNA-binding surface important for scanning function.
abstract: The translation initiation factor eIF1A is necessary for directing the 43S preinitiation complex from the 5' end of the mRNA to the initiation codon in a process termed scanning. We have determined the solution structure of human eIF1A, which reveals an oligonucleotide-binding (OB) fold and an additional domain. NMR titration experiments showed that eIF1A binds single-stranded RNA oligonucleotides in a site-specific, but non-sequence-specific manner, hinting at an mRNA interaction rather than specific rRNA or tRNA binding. The RNA binding surface extends over a large area covering the canonical OB fold binding site as well as a groove leading to the second domain. Site-directed mutations at multiple positions along the RNA-binding surface were defective in the ability to properly assemble preinitiation complexes at the AUG codon in vitro.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Battiste
authors.forename: T V
authors.initials: TV
authors.lastname: Pestova
authors.forename: C U
authors.initials: CU
authors.lastname: Hellen
authors.forename: G
authors.initials: G
authors.lastname: Wagner
mesh_terms: D000595:Amino Acid Sequence; D001105:Archaea; D001419:Bacteria; D001483:Base Sequence; D001665:Binding Sites; D003062:Codon; D015977:Eukaryotic Initiation Factor-1; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009843:Oligoribonucleotides / Q000737:chemistry* / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D013379:Substrate Specificity
chemical_list: D003062:Codon; D015977:Eukaryotic Initiation Factor-1; D009843:Oligoribonucleotides; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012996:Solutions; C026022:eukaryotic peptide initiation factor-1A