Spatial structure of disordered proteins dictates conductance and selectivity in nuclear pore complex mimics

Adithya N Ananth, Ankur Mishra, Steffen Frey, Arvind Dwarkasing, Roderick Versloot, Erik van der Giessen, Dirk Görlich, Patrick Onck, Cees Dekker

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Nuclear pore complexes (NPCs) lined with intrinsically disordered FG-domains act as selective gatekeepers for molecular transport between the nucleus and the cytoplasm in eukaryotic cells. The underlying physical mechanism of the intriguing selectivity is still under debate. Here, we probe the transport of ions and transport receptors through biomimetic NPCs consisting of Nsp1 domains attached to the inner surface of solid-state nanopores. We examine both wildtype FG-domains and hydrophilic SG-mutants. FG-nanopores showed a clear selectivity as transport receptors can translocate across the pore whereas other proteins cannot. SG mutant pores lack such selectivity. To unravel this striking difference, we present coarse-grained molecular dynamics simulations that reveal that FG-pores exhibit a high-density, nonuniform protein distribution, in contrast to a uniform and significantly less-dense protein distribution in the SG-mutant. We conclude that the sequence-dependent density distribution of disordered proteins inside the NPC plays a key role for its conductivity and selective permeability.

Original languageEnglish
Article number31510
Number of pages24
JournaleLife
Volume7
Early online date14-Feb-2018
DOIs
Publication statusPublished - 14-Feb-2018

Keywords

  • SOLID-STATE NANOPORES
  • MOLECULAR-DYNAMICS SIMULATIONS
  • TRANSPORT
  • TRANSLOCATION
  • PERMEABILITY
  • NUCLEOPORINS
  • MECHANISM
  • ARCHITECTURE
  • HYDROGEL
  • REPEATS

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