Structural basis of the nic96 subcomplex organization in the nuclear pore channel

Mol Cell. 2008 Jan 18;29(1):46-55. doi: 10.1016/j.molcel.2007.10.022.

Abstract

Nic96 is a conserved nucleoporin that recruits the Nsp1-Nup49-Nup57 complex, a module with Phe-Gly (FG) repeats, to the central transport channel of the nuclear pore complex (NPC). Nic96 binds the Nsp1 complex via its N domain and assembles into the NPC framework via its central and C domain. Here, we report the crystal structure of a large structural nucleoporin, Nic96 without its N domain (Nic96DeltaN). Nic96DeltaN is composed of three domains and is a straight molecule that--although almost entirely helical--exhibits strong deviations from the predicted alpha-solenoid fold. The missing N domain projects midway from the Nic96 molecule, indicating how the Nsp1 complex might be located with respect to the rod-like Nic96. Notably, Nic96DeltaN binds in vitro to FG repeats of the Nsp1 complex. These data suggest a model of how Nic96 could organize a transport module with coiled-coil domains and FG repeats in the central pore channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins / chemistry*
  • Calcium-Binding Proteins / ultrastructure
  • Crystallography, X-Ray
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / ultrastructure
  • Microscopy, Electron
  • Models, Molecular
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / ultrastructure
  • Nuclear Pore / chemistry*
  • Nuclear Pore / ultrastructure
  • Nuclear Pore Complex Proteins / chemistry*
  • Nuclear Pore Complex Proteins / ultrastructure
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / ultrastructure
  • Point Mutation
  • Protein Conformation
  • Protein Interaction Mapping*
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Repetitive Sequences, Amino Acid
  • Saccharomyces cerevisiae / chemistry*
  • Saccharomyces cerevisiae / ultrastructure
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / ultrastructure
  • Structure-Activity Relationship

Substances

  • Calcium-Binding Proteins
  • Membrane Proteins
  • Multiprotein Complexes
  • NIC96 protein, S cerevisiae
  • NSP1 protein, S cerevisiae
  • NUP49 protein, S cerevisiae
  • NUP57 protein, S cerevisiae
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins

Associated data

  • PDB/2RFO