title: Probing the disordered domain of the nuclear pore complex through coarse-grained molecular dynamics simulations.
abstract: The distribution of disordered proteins (FG-nups) that line the transport channel of the nuclear pore complex (NPC) is investigated by means of coarse-grained molecular dynamics simulations. A one-bead-per-amino-acid model is presented that accounts for the hydrophobic/hydrophilic and electrostatic interactions between different amino acids, polarity of the solvent, and screening of free ions. The results indicate that the interaction of the FG-nups forms a high-density, doughnut-like distribution inside the NPC, which is rich in FG-repeats. We show that the obtained distribution is encoded in the amino-acid sequence of the FG-nups and is driven by both electrostatic and hydrophobic interactions. To explore the relation between structure and function, we have systematically removed different combinations of FG-nups from the pore to simulate inviable and viable NPCs that were previously studied experimentally. The obtained density distributions show that the maximum density of the FG-nups inside the pore does not exceed 185 mg/mL in the inviable NPCs, whereas for the wild-type and viable NPCs, this value increases to 300 mg/mL. Interestingly, this maximum density is not correlated to the total mass of the FG-nups, but depends sensitively on the specific combination of essential Nups located in the central plane of the NPC.
authors.affiliation: Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands.
authors.forename: Ali
authors.initials: A
authors.lastname: Ghavami
authors.affiliation: European Institute for the Biology of Ageing, University of Groningen, Groningen, The Netherlands.
authors.forename: Liesbeth M
authors.initials: LM
authors.lastname: Veenhoff
authors.affiliation: Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: van der Giessen
authors.affiliation: Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands. Electronic address: p.r.onck@rug.nl.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Onck
mesh_terms: D002470:Cell Survival; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D020449:Repetitive Sequences, Amino Acid; D055672:Static Electricity
chemical_list: D005656:Fungal Proteins; D028861:Nuclear Pore Complex Proteins