title: Simple biophysics underpins collective conformations of the intrinsically disordered proteins of the Nuclear Pore Complex.
abstract: Nuclear Pore Complexes (NPCs) are key cellular transporter that control nucleocytoplasmic transport in eukaryotic cells, but its transport mechanism is still not understood. The centerpiece of NPC transport is the assembly of intrinsically disordered polypeptides, known as FG nucleoporins, lining its passageway. Their conformations and collective dynamics during transport are difficult to assess in vivo. In vitro investigations provide partially conflicting results, lending support to different models of transport, which invoke various conformational transitions of the FG nucleoporins induced by the cargo-carrying transport proteins. We show that the spatial organization of FG nucleoporin assemblies with the transport proteins can be understood within a first principles biophysical model with a minimal number of key physical variables, such as the average protein interaction strengths and spatial densities. These results address some of the outstanding controversies and suggest how molecularly divergent NPCs in different species can perform essentially the same function.
authors.affiliation: Department of Physics, University of Toronto, Toronto, Canada.
authors.forename: Andrei
authors.initials: A
authors.lastname: Vovk
authors.affiliation: Department of Physics, University of Toronto, Toronto, Canada.
authors.forename: Chad
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, United States.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Opferman
authors.affiliation: Biozentrum and the Swiss Nanoscience Institute, University of Basel, Basel, Switzerland.
authors.forename: Larisa E
authors.initials: LE
authors.lastname: Kapinos
authors.affiliation: Biozentrum and the Swiss Nanoscience Institute, University of Basel, Basel, Switzerland.
authors.forename: Roderick Yh
authors.initials: RY
authors.lastname: Lim
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, United States.
authors.forename: Rob D
authors.initials: RD
authors.lastname: Coalson
authors.affiliation: Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, United States.
authors.forename: David
authors.initials: D
authors.lastname: Jasnow
authors.affiliation: Department of Physics, University of Toronto, Toronto, Canada.|Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
authors.forename: Anton
authors.identifier: 0000-0002-8523-6703
authors.initials: A
authors.lastname: Zilman
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D008962:Models, Theoretical; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D064267:Intrinsically Disordered Proteins; D028861:Nuclear Pore Complex Proteins
keywords: biophysics; computational biology; intrinsically disordered proteins; none; nulcear pore complex; phase separation; polymers; structural biology; systems biology; theory