Long unfolded linkers facilitate membrane protein import through the nuclear pore complex

Science. 2011 Jul 1;333(6038):90-3. doi: 10.1126/science.1205741. Epub 2011 Jun 9.

Abstract

Active nuclear import of soluble cargo involves transport factors that shuttle cargo through the nuclear pore complex (NPC) by binding to phenylalanine-glycine (FG) domains. How nuclear membrane proteins cross through the NPC to reach the inner membrane is presently unclear. We found that at least a 120-residue-long intrinsically disordered linker was required for the import of membrane proteins carrying a nuclear localization signal for the transport factor karyopherin-α. We propose an import mechanism for membrane proteins in which an unfolded linker slices through the NPC scaffold to enable binding between the transport factor and the FG domains in the center of the NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • Endoplasmic Reticulum / metabolism
  • Karyopherins / chemistry
  • Karyopherins / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • Nuclear Envelope / metabolism*
  • Nuclear Localization Signals
  • Nuclear Pore / metabolism*
  • Nuclear Pore Complex Proteins / chemistry
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein Folding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Heh2 protein, S cerevisiae
  • Karyopherins
  • Membrane Proteins
  • NSP1 protein, S cerevisiae
  • NUP100 protein, S cerevisiae
  • NUP145 protein, S cerevisiae
  • NUP57 protein, S cerevisiae
  • Nuclear Localization Signals
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Srp1 protein, S cerevisiae