title: Architecture of the symmetric core of the nuclear pore.
abstract: The nuclear pore complex (NPC) controls the transport of macromolecules between the nucleus and cytoplasm, but its molecular architecture has thus far remained poorly defined. We biochemically reconstituted NPC core protomers and elucidated the underlying protein-protein interaction network. Flexible linker sequences, rather than interactions between the structured core scaffold nucleoporins, mediate the assembly of the inner ring complex and its attachment to the NPC coat. X-ray crystallographic analysis of these scaffold nucleoporins revealed the molecular details of their interactions with the flexible linker sequences and enabled construction of full-length atomic structures. By docking these structures into the cryoelectron tomographic reconstruction of the intact human NPC and validating their placement with our nucleoporin interactome, we built a composite structure of the NPC symmetric core that contains ~320,000 residues and accounts for ~56 megadaltons of the NPC's structured mass. Our approach provides a paradigm for the structure determination of similarly complex macromolecular assemblies.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lin
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Stuwe
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schilbach
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Rundlet
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Perriches
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: George
authors.initials: G
authors.lastname: Mobbs
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Karsten
authors.initials: K
authors.lastname: Thierbach
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Ferdinand M
authors.initials: FM
authors.lastname: Huber
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Leslie N
authors.initials: LN
authors.lastname: Collins
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Davenport
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Young E
authors.initials: YE
authors.lastname: Jeon
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA. hoelz@caltech.edu.
authors.forename: André
authors.initials: A
authors.lastname: Hoelz
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism; D055032:Electron Microscope Tomography; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D022022:Nuclear Pore / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D060066:Protein Interaction Maps; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D028861:Nuclear Pore Complex Proteins; D021122:Protein Subunits