title: Translocation through the nuclear pore complex: selectivity and speed by reduction-of-dimensionality.
abstract: Translocation through the nuclear pore complex (NPC), a large transporter spanning the nuclear envelope, is a passive, diffusion-driven process, paradoxically enhanced by binding. To account for this mystery, several models have been suggested. However, recent experiments with modified NPCs make reconsideration necessary. Here, we suggest that nuclear transport receptors (NTRs) such as the karyopherins, in accordance with their peculiar boat-like structure, act as nanoscopic ferries transporting cargos through the NPC by sliding on a surface of phenylalanine glycine (FG) motifs. The dense array of FG motifs that covers the cytoplasmic filaments of the NPC is thought to continue on the wall of the large channel permeating the central framework of the NPC and on parts of the nuclear filaments to yield a coherent FG surface. Nuclear transport receptors are assumed to bind to the FG surface at filaments or at the channel entrance and then to rapidly search the FG surface by a two-dimensional random walk for the channel exit where they are released. The passage of neutral molecules is restricted to a narrow tube in the center of the central channel by a loose network of peptide chains. The model features virtual gating, is compatible with but not dependent on FG affinity gradients and tolerates deletions and transpositions of FG motifs. Implications of the model are discussed and tests are suggested.
authors.affiliation: Institute of Medical Physics and Biophysics and Center of Nanotechnology (CeNTech), University of Muenster, Robert-Koch-Strasse 31, 48149 Muenster, Germany. petersr@uni-muenster.de
authors.forename: Reiner
authors.initials: R
authors.lastname: Peters
mesh_terms: D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004058:Diffusion; D005544:Forecasting; D005998:Glycine / Q000235:genetics; D028884:Karyopherins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D049329:Nanostructures; D009685:Nuclear Envelope / Q000378:metabolism; D022022:Nuclear Pore / Q000737:chemistry / Q000378:metabolism*; D010649:Phenylalanine / Q000235:genetics; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D028884:Karyopherins; D010649:Phenylalanine; D005998:Glycine