title: Molecular architecture of the 40S⋅eIF1⋅eIF3 translation initiation complex.
abstract: Eukaryotic translation initiation requires the recruitment of the large, multiprotein eIF3 complex to the 40S ribosomal subunit. We present X-ray structures of all major components of the minimal, six-subunit Saccharomyces cerevisiae eIF3 core. These structures, together with electron microscopy reconstructions, cross-linking coupled to mass spectrometry, and integrative structure modeling, allowed us to position and orient all eIF3 components on the 40S⋅eIF1 complex, revealing an extended, modular arrangement of eIF3 subunits. Yeast eIF3 engages 40S in a clamp-like manner, fully encircling 40S to position key initiation factors on opposite ends of the mRNA channel, providing a platform for the recruitment, assembly, and regulation of the translation initiation machinery. The structures of eIF3 components reported here also have implications for understanding the architecture of the mammalian 43S preinitiation complex and the complex of eIF3, 40S, and the hepatitis C internal ribosomal entry site RNA.
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Otto-Stern-Weg 5, 8093 Zurich, Switzerland. Electronic address: jan.erzberger@mol.biol.ethz.ch.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Erzberger
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, 8093 Zurich, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Stengel
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences (QB3), University of California, San Francisco, UCSF MC 2552, Byers Hall Room 503B, 1700 4th Street, San Francisco, CA 94158-2330, USA.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pellarin
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Otto-Stern-Weg 5, 8093 Zurich, Switzerland.
authors.forename: Suyang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Otto-Stern-Weg 5, 8093 Zurich, Switzerland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schaefer
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Otto-Stern-Weg 5, 8093 Zurich, Switzerland.
authors.forename: Christopher H S
authors.initials: CHS
authors.lastname: Aylett
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences (QB3), University of California, San Francisco, UCSF MC 2552, Byers Hall Room 503B, 1700 4th Street, San Francisco, CA 94158-2330, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Cimermančič
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Otto-Stern-Weg 5, 8093 Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Boehringer
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences (QB3), University of California, San Francisco, UCSF MC 2552, Byers Hall Room 503B, 1700 4th Street, San Francisco, CA 94158-2330, USA.
authors.forename: Andrej
authors.initials: A
authors.lastname: Sali
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, 8093 Zurich, Switzerland; Faculty of Science, University of Zurich, 8006 Zurich, Switzerland.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.affiliation: Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Otto-Stern-Weg 5, 8093 Zurich, Switzerland. Electronic address: ban@mol.biol.ethz.ch.
authors.forename: Nenad
authors.initials: N
authors.lastname: Ban
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D019281:Dimerization; D015977:Eukaryotic Initiation Factor-1 / Q000737:chemistry* / Q000378:metabolism; D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry* / Q000378:metabolism; D016174:Hepacivirus / Q000737:chemistry; D006801:Humans; D008322:Mammals / Q000378:metabolism; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational; D012261:Ribonucleoproteins / Q000737:chemistry; D054682:Ribosome Subunits, Small, Eukaryotic / Q000737:chemistry* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D015977:Eukaryotic Initiation Factor-1; D039621:Eukaryotic Initiation Factor-3; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins