Probing the Disordered Domain of the Nuclear Pore Complex through Coarse-Grained Molecular Dynamics Simulations

Ali Ghavami, Liesbeth M. Veenhoff, Erik van der Giessen, Patrick R. Onck*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

52 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)1393-1402
Number of pages10
JournalBiophysical Journal
Volume107
Issue number6
DOIs
Publication statusPublished - 16-Sep-2014

Keywords

  • NUCLEOCYTOPLASMIC TRANSPORT
  • FG NUCLEOPORINS
  • REPEAT REGIONS
  • IMPORTIN-BETA
  • ARCHITECTURE
  • TRANSLOCATION
  • PROTEINS
  • CHANNEL
  • BINDING
  • MODEL

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