title: Assembly of eIF3 Mediated by Mutually Dependent Subunit Insertion.
abstract: Eukaryotic initiation factor 3 (eIF3), an essential multi-protein complex involved in translation initiation, is composed of 12 tightly associated subunits in humans. While the overall structure of eIF3 is known, the mechanism of its assembly and structural consequences of dysregulation of eIF3 subunit expression seen in many cancers is largely unknown. Here we show that subunits in eIF3 assemble into eIF3 in an interdependent manner. Assembly of eIF3 is governed primarily by formation of a helical bundle, composed of helices extending C-terminally from PCI-MPN domains in eight subunits. We propose that, while the minimal subcomplex of human-like eIF3 functional for translation initiation in cells consists of subunits a, b, c, f, g, i, and m, numerous other eIF3 subcomplexes exist under circumstances of subunit over- or underexpression. Thus, eIF3 subcomplexes formed or "released" due to dysregulated subunit expression may be determining factors contributing to eIF3-related cancers.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: M Duane
authors.initials: MD
authors.lastname: Smith
authors.affiliation: Graduate Group in Comparative Biochemistry, University of California, Berkeley, CA 94720, USA.
authors.forename: Luisa
authors.initials: L
authors.lastname: Arake-Tacca
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Nitido
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Montabana
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: Annsea
authors.initials: A
authors.lastname: Park
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Graduate Group in Comparative Biochemistry, University of California, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, CA 94720, USA; Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: jcate@lbl.gov.
authors.forename: Jamie H
authors.initials: JH
authors.lastname: Cate
mesh_terms: D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry* / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008958:Models, Molecular; D009492:Neurospora crassa / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
chemical_list: D039621:Eukaryotic Initiation Factor-3; D005656:Fungal Proteins