title: Cargo surface hydrophobicity is sufficient to overcome the nuclear pore complex selectivity barrier.
abstract: To fulfil their function, nuclear pore complexes (NPCs) must discriminate between inert proteins and nuclear transport receptors (NTRs), admitting only the latter. This specific permeation is thought to depend on interactions between hydrophobic patches on NTRs and phenylalanine-glycine (FG) or related repeats that line the NPC. Here, we tested this premise directly by conjugating different hydrophobic amino-acid analogues to the surface of an inert protein and examining its ability to cross NPCs unassisted by NTRs. Conjugation of as few as four hydrophobic moieties was sufficient to enable passage of the protein through NPCs. Transport of the modified protein proceeded with rates comparable to those measured for the innate protein when bound to an NTR and was relatively insensitive both to the nature and density of the amino acids used to confer hydrophobicity. The latter observation suggests a non-specific, small, and plant interaction network between cargo and FG repeats.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Bracha
authors.initials: B
authors.lastname: Naim
authors.forename: David
authors.initials: D
authors.lastname: Zbaida
authors.forename: Shlomi
authors.initials: S
authors.lastname: Dagan
authors.forename: Ruti
authors.initials: R
authors.lastname: Kapon
authors.forename: Ziv
authors.initials: Z
authors.lastname: Reich
mesh_terms: D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002467:Cell Nucleus / Q000378:metabolism; D016000:Cluster Analysis; D005998:Glycine / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D022022:Nuclear Pore / Q000378:metabolism*; D010539:Permeability; D010649:Phenylalanine / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013499:Surface Properties
chemical_list: D012710:Serum Albumin, Bovine; D010649:Phenylalanine; D005998:Glycine
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