title: Molecular architecture of a eukaryotic translational initiation complex.
abstract: The last step in eukaryotic translational initiation involves the joining of the large and small subunits of the ribosome, with initiator transfer RNA (Met-tRNA(i)(Met)) positioned over the start codon of messenger RNA in the P site. This step is catalyzed by initiation factor eIF5B. We used recent advances in cryo-electron microscopy (cryo-EM) to determine a structure of the eIF5B initiation complex to 6.6 angstrom resolution from <3% of the population, comprising just 5143 particles. The structure reveals conformational changes in eIF5B, initiator tRNA, and the ribosome that provide insights into the role of eIF5B in translational initiation. The relatively high resolution obtained from such a small fraction of a heterogeneous sample suggests a general approach for characterizing the structure of other dynamic or transient biological complexes.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, CB2 0QH, United Kingdom.
authors.forename: Israel S
authors.initials: IS
authors.lastname: Fernández
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, CB2 0QH, United Kingdom.
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Bai
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, CB2 0QH, United Kingdom.
authors.forename: Tanweer
authors.initials: T
authors.lastname: Hussain
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, CB2 0QH, United Kingdom.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Kelley
authors.affiliation: Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, USA.
authors.forename: Jon R
authors.initials: JR
authors.lastname: Lorsch
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, CB2 0QH, United Kingdom.
authors.forename: V
authors.initials: V
authors.lastname: Ramakrishnan
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, CB2 0QH, United Kingdom.
authors.forename: Sjors H W
authors.initials: SHW
authors.lastname: Scheres
mesh_terms: D053000:Analytic Sample Preparation Methods; D020285:Cryoelectron Microscopy / Q000379:methods; D039642:Eukaryotic Initiation Factors / Q000737:chemistry*; D006801:Humans; D010442:Peptide Chain Initiation, Translational; D011487:Protein Conformation; D012358:RNA, Transfer, Met / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry*; D012441:Saccharomyces cerevisiae
chemical_list: D039642:Eukaryotic Initiation Factors; D012358:RNA, Transfer, Met; C451459:eukaryotic initiation factor-5B