title: Molecular architecture of the inner ring scaffold of the human nuclear pore complex.
abstract: Nuclear pore complexes (NPCs) are 110-megadalton assemblies that mediate nucleocytoplasmic transport. NPCs are built from multiple copies of ~30 different nucleoporins, and understanding how these nucleoporins assemble into the NPC scaffold imposes a formidable challenge. Recently, it has been shown how the Y complex, a prominent NPC module, forms the outer rings of the nuclear pore. However, the organization of the inner ring has remained unknown until now. We used molecular modeling combined with cross-linking mass spectrometry and cryo-electron tomography to obtain a composite structure of the inner ring. This architectural map explains the vast majority of the electron density of the scaffold. We conclude that despite obvious differences in morphology and composition, the higher-order structure of the inner and outer rings is unexpectedly similar.
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kosinski
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Shyamal
authors.initials: S
authors.lastname: Mosalaganti
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: von Appen
authors.affiliation: Biochemistry Center of Heidelberg University, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Teimer
authors.affiliation: Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, 507 River Street, Hoboken, NJ 07030, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: DiGuilio
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: William
authors.initials: W
authors.lastname: Wan
authors.affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
authors.forename: Khanh Huy
authors.initials: KH
authors.lastname: Bui
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Wim J H
authors.initials: WJ
authors.lastname: Hagen
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. Cell Biology and Biophysics Unit, EMBL, Heidelberg, Germany.
authors.forename: John A G
authors.initials: JA
authors.lastname: Briggs
authors.affiliation: Department of Chemistry, Chemical Biology and Biomedical Engineering, Stevens Institute of Technology, 507 River Street, Hoboken, NJ 07030, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Glavy
authors.affiliation: Biochemistry Center of Heidelberg University, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany.
authors.forename: Ed
authors.initials: E
authors.lastname: Hurt
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. Cell Biology and Biophysics Unit, EMBL, Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Beck
mesh_terms: D021581:Active Transport, Cell Nucleus; D020285:Cryoelectron Microscopy; D055032:Electron Microscope Tomography; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D008958:Models, Molecular; D015530:Nuclear Matrix / Q000378:metabolism / Q000648:ultrastructure; D022022:Nuclear Pore / Q000378:metabolism* / Q000648:ultrastructure*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D028861:Nuclear Pore Complex Proteins; C508154:Nup93 protein, human