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

eLife

Cees Dekker¹  Roderick Versloot¹  Adithya N Ananth¹  Arvind Dwarkasing¹  Steffen Frey²  Dirk Görlich²  Erik van der Giessen³  Patrick Onck³  Ankur Mishra³ 

[1] Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands;Max Planck Institute for Biophysical Chemistry, Göttingen, Germany;Zernike Institute for Advanced Materials, University of Groningen, Groningen, Netherlands;

关键词: Nuclear Pore Complex;    FG-Nups;    solid-state nanopores;    selective barrier;   

DOI  :  10.7554/eLife.31510

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown