title: The permeability barrier of nuclear pore complexes appears to operate via hydrophobic exclusion.
abstract: Nuclear pore complexes (NPCs) restrict the nucleocytoplasmic flux of most macromolecules, but permit facilitated passage of nuclear transport receptors and their cargo complexes. We found that a simple hydrophobic interaction column can mimic the selectivity of NPCs surprisingly well and that nuclear transport receptors appear to be the most hydrophobic soluble proteins. This suggests that surface hydrophobicity represents a major sorting criterion of NPCs. The rate of NPC passage of cargo-receptor complexes is, however, not dominated just by properties of the receptors. We found that large cargo domains drastically hinder NPC passage and require more than one receptor molecule for rapid translocation. This argues against a rigid translocation channel and instead suggests that NPC passage involves a partitioning of the entire translocating species into a hydrophobic phase, whereby the receptor:cargo ratio determines the solubility in that permeability barrier. Finally, we show that interfering with hydrophobic interactions causes a reversible collapse of the permeability barrier of NPCs, which is consistent with the assumption that the barrier is formed by phenylalanine-rich nucleoporin repeats that attract each other through hydrophobic interactions.
authors.affiliation: ZMBH, INF 282, D-69120 Heidelberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Ribbeck
authors.forename: Dirk
authors.initials: D
authors.lastname: Görlich
mesh_terms: D020816:Amino Acid Motifs; D002467:Cell Nucleus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008857:Microscopy, Interference; D008954:Models, Biological; D022022:Nuclear Pore / Q000737:chemistry; D010539:Permeability; D010649:Phenylalanine / Q000737:chemistry; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D028961:beta Karyopherins / Q000378:metabolism
chemical_list: D028884:Karyopherins; D011994:Recombinant Proteins; D028961:beta Karyopherins; D010649:Phenylalanine