title: Structure and Function of the Nuclear Pore Complex Cytoplasmic mRNA Export Platform.
abstract: The last steps in mRNA export and remodeling are performed by the Nup82 complex, a large conserved assembly at the cytoplasmic face of the nuclear pore complex (NPC). By integrating diverse structural data, we have determined the molecular architecture of the native Nup82 complex at subnanometer precision. The complex consists of two compositionally identical multiprotein subunits that adopt different configurations. The Nup82 complex fits into the NPC through the outer ring Nup84 complex. Our map shows that this entire 14-MDa Nup82-Nup84 complex assembly positions the cytoplasmic mRNA export factor docking sites and messenger ribonucleoprotein (mRNP) remodeling machinery right over the NPC's central channel rather than on distal cytoplasmic filaments, as previously supposed. We suggest that this configuration efficiently captures and remodels exporting mRNP particles immediately upon reaching the cytoplasmic side of the NPC.
authors.affiliation: Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Fernandez-Martinez
authors.affiliation: Departments of Bioengineering and Therapeutic Sciences and Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Seung Joong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Upla
authors.affiliation: Departments of Bioengineering and Therapeutic Sciences and Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Structural Bioinformatics Unit, Institut Pasteur, CNRS UMR 3528, 75015 Paris, France.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pellarin
authors.affiliation: Département de Biochimie et Médecine Moléculaire, University of Montréal, Montréal, QC H3C3J7, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Gagnon
authors.affiliation: Departments of Bioengineering and Therapeutic Sciences and Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Ilan E
authors.initials: IE
authors.lastname: Chemmama
authors.affiliation: Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Junjie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Ilona
authors.initials: I
authors.lastname: Nudelman
authors.affiliation: Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Wenzhu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Williams
authors.affiliation: Simons Electron Microscopy Center at New York Structural Biology Center, New York, NY 10027, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Rice
authors.affiliation: Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Stokes
authors.affiliation: Département de Biochimie et Médecine Moléculaire, University of Montréal, Montréal, QC H3C3J7, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zenklusen
authors.affiliation: Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065, USA. Electronic address: chait@rockefeller.edu.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Chait
authors.affiliation: Departments of Bioengineering and Therapeutic Sciences and Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: sali@salilab.org.
authors.forename: Andrej
authors.initials: A
authors.lastname: Sali
authors.affiliation: Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY 10065, USA. Electronic address: rout@rockefeller.edu.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Rout
mesh_terms: D021581:Active Transport, Cell Nucleus; D005656:Fungal Proteins; D022022:Nuclear Pore / Q000737:chemistry*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000648:ultrastructure; D012333:RNA, Messenger; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000648:ultrastructure; D015003:Yeasts / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins
keywords: Nup4 complex; Nup82 complex; computational structural biology; cross-linking and mass spectrometry; electron microscopy; integrative structure determination; mRNA export; mRNP remodeling; nuclear pore complex; small-angle X-ray scattering