title: Architecture of human translation initiation factor 3.
abstract: Eukaryotic translation initiation factor 3 (eIF3) plays a central role in protein synthesis by organizing the formation of the 43S preinitiation complex. Using genetic tag visualization by electron microscopy, we reveal the molecular organization of ten human eIF3 subunits, including an octameric core. The structure of eIF3 bears a close resemblance to that of the proteasome lid, with a conserved spatial organization of eight core subunits containing PCI and MPN domains that coordinate functional interactions in both complexes. We further show that eIF3 subunits a and c interact with initiation factors eIF1 and eIF1A, which control the stringency of start codon selection. Finally, we find that subunit j, which modulates messenger RNA interactions with the small ribosomal subunit, makes multiple independent interactions with the eIF3 octameric core. These results highlight the conserved architecture of eIF3 and how it scaffolds key factors that control translation initiation in higher eukaryotes, including humans.
authors.affiliation: Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California-Berkeley, Berkeley, CA 94720, USA.
authors.forename: Jordi
authors.initials: J
authors.lastname: Querol-Audi
authors.forename: Chaomin
authors.initials: C
authors.lastname: Sun
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Vogan
authors.forename: M Duane
authors.initials: MD
authors.lastname: Smith
authors.forename: Yu
authors.initials: Y
authors.lastname: Gu
authors.forename: Jamie H D
authors.initials: JH
authors.lastname: Cate
authors.forename: Eva
authors.initials: E
authors.lastname: Nogales
mesh_terms: D001704:Biopolymers / Q000737:chemistry; D018387:Codon, Initiator; D020285:Cryoelectron Microscopy; D006801:Humans; D039665:Prokaryotic Initiation Factor-3 / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D001704:Biopolymers; D018387:Codon, Initiator; D039665:Prokaryotic Initiation Factor-3