scholarly journals Intrinsically disordered nuclear pore proteins show ideal-polymer morphologies and dynamics

2019 ◽  
Author(s):  
Luke K. Davis ◽  
Ian J. Ford ◽  
Anđela Šarić ◽  
Bart W. Hoogenboom
Keyword(s):  
Nuclear Pore Complex ◽  
Polymer Brush ◽  
Polymer Chains ◽  
Nuclear Pore ◽  
Computational Simulations ◽  
Crossover Point ◽  
Transport Barrier ◽  
Intrinsically Disordered ◽  
Wide Range ◽  
Nuclear Pore Proteins

In the nuclear pore complex (NPC), intrinsically disordered nuclear pore proteins (FG nups) form a selective barrier for transport into and out of the cell nucleus, in a way that remains poorly understood. The collective FG nup behaviour has long been conceptualized either as a polymer brush, dominated by entropic and excluded-volume (repulsive) interactions, or as a hydrogel, dominated by cohesive (attractive) interactions between FG nups. Here we compare mesoscale computational simulations with a wide range of experimental data to demonstrate that FG nups are at the crossover point between these two regimes. Specifically, we find that repulsive and attractive interactions are balanced, resulting in morphologies and dynamics that are close to those of ideal polymer chains. We demonstrate that this property of FG nups yields sufficient cohesion to seal the transport barrier, and yet maintains fast dynamics at the molecular scale, permitting the rapid polymer rearrangements needed for transport events.

scholarly journals Mapping the native organization of the yeast nuclear pore complex using nuclear radial intensity measurements

2019 ◽  
Vol 116 (29) ◽  
pp. 14606-14613 ◽  
Author(s):  
Pascal Vallotton ◽  
Sasikumar Rajoo ◽  
Matthias Wojtynek ◽  
Evgeny Onischenko ◽  
Annemarie Kralt ◽  
...  
Keyword(s):  
Nuclear Pore Complex ◽  
Nucleocytoplasmic Transport ◽  
Live Cells ◽  
Nuclear Pore ◽  
Intrinsically Disordered ◽  
Intensity Measurements ◽  
Composition And Structure ◽  
Associated Proteins ◽  
Multiple Copies

Selective transport across the nuclear envelope (NE) is mediated by the nuclear pore complex (NPC), a massive ∼100-MDa assembly composed of multiple copies of ∼30 nuclear pore proteins (Nups). Recent advances have shed light on the composition and structure of NPCs, but approaches that could map their organization in live cells are still lacking. Here, we introduce an in vivo method to perform nuclear radial intensity measurements (NuRIM) using fluorescence microscopy to determine the average position of NE-localized proteins along the nucleocytoplasmic transport axis. We apply NuRIM to study the organization of the NPC and the mobile transport machinery in budding yeast. This reveals a unique snapshot of the intact yeast NPC and identifies distinct steady-state localizations for various NE-associated proteins and nuclear transport factors. We find that the NPC architecture is robust against compositional changes and could also confirm that in contrast to Chlamydomonas reinhardtii, the scaffold Y complex is arranged symmetrically in the yeast NPC. Furthermore, NuRIM was applied to probe the orientation of intrinsically disordered FG-repeat segments, providing insight into their roles in selective NPC permeability and structure.

scholarly journals A Study of Intrinsically Disordered Proteins from Nuclear Pore Complex

2013 ◽  
Vol 104 (2) ◽  
pp. 55a-56a
Author(s):  
Jianhui Tian ◽  
Anton Zilman ◽  
Sandrasegaram Gnanakaran
Keyword(s):  
Nuclear Pore Complex ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Intrinsically Disordered

scholarly journals Intrinsically disordered nuclear pore proteins show ideal-polymer morphologies and dynamics

2020 ◽  
Vol 101 (2) ◽  
Author(s):  
Luke K. Davis ◽  
Ian J. Ford ◽  
Anđela Šarić ◽  
Bart W. Hoogenboom
Keyword(s):  
Nuclear Pore ◽  
Intrinsically Disordered ◽  
Nuclear Pore Proteins

scholarly journals A designer FG-Nup that reconstitutes the selective transport barrier of the nuclear pore complex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alessio Fragasso ◽  
Hendrik W. de Vries ◽  
John Andersson ◽  
Eli O. van der Sluis ◽  
Erik van der Giessen ◽  
...  
Keyword(s):  
Coarse Grained ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Transport Barrier ◽  
Selective Transport ◽  
Intrinsically Disordered ◽  
Bidirectional Transport ◽  
Dynamics Simulations ◽  
Pore Complexes ◽  
Transport Receptor

AbstractNuclear Pore Complexes (NPCs) regulate bidirectional transport between the nucleus and the cytoplasm. Intrinsically disordered FG-Nups line the NPC lumen and form a selective barrier, where transport of most proteins is inhibited whereas specific transporter proteins freely pass. The mechanism underlying selective transport through the NPC is still debated. Here, we reconstitute the selective behaviour of the NPC bottom-up by introducing a rationally designed artificial FG-Nup that mimics natural Nups. Using QCM-D, we measure selective binding of the artificial FG-Nup brushes to the transport receptor Kap95 over cytosolic proteins such as BSA. Solid-state nanopores with the artificial FG-Nups lining their inner walls support fast translocation of Kap95 while blocking BSA, thus demonstrating selectivity. Coarse-grained molecular dynamics simulations highlight the formation of a selective meshwork with densities comparable to native NPCs. Our findings show that simple design rules can recapitulate the selective behaviour of native FG-Nups and demonstrate that no specific spacer sequence nor a spatial segregation of different FG-motif types are needed to create selective NPCs.

scholarly journals Physical modelling of multivalent interactions in the nuclear pore complex

2020 ◽  
Author(s):  
Luke K. Davis ◽  
Anđela Šarić ◽  
Bart W. Hoogenboom ◽  
Anton Zilman
Keyword(s):  
Experimental Data ◽  
Single Molecule ◽  
Nuclear Pore Complex ◽  
Intrinsically Disordered Proteins ◽  
Binding Kinetics ◽  
Disordered Proteins ◽  
Minor Role ◽  
Nuclear Pore ◽  
Minimal Models ◽  
Intrinsically Disordered

In the nuclear pore complex (NPC), intrinsically disordered proteins (FG Nups) along with their interactions with more globular proteins called nuclear transport receptors (NTRs) are vital to the selectivity of transport into and out of the cell nucleus. While such interactions can be modelled at different levels of coarse graining, in-vitro experimental data have been quantitatively described by minimal models that describe FG Nups as cohesive homogeneous polymers and NTRs as uniformly cohesive spheres, where the heterogeneous effects have been smeared out. By definition, these minimal models do not account for the explicit heterogeneities in FG Nup sequences, essentially a string of cohesive and non-cohesive polymer units, and at the NTR surface. Here, we develop computational and analytical models that do take into account such heterogeneity at a level of minimal complexity, and compare them to experimental data on single-molecule interactions between FG Nups and NTRs. Overall, we find that the heterogeneous nature of FG Nups and NTRs plays a minor role for their equilibrium binding properties, but is of significance when it comes to (un)binding kinetics. Using our models, we predict how binding equilibria and kinetics depend on the distribution of cohesive blocks in the FG Nup sequences and of the binding pockets at the NTR surface, with multivalency playing a key role. Finally, we observe that single-molecule binding kinetics has a rather minor influence on the diffusion of NTRs in polymer melts consisting of FG-Nup-like sequences.

scholarly journals Intrinsically Disordered Proteins: Gatekeepers of the Nuclear Pore Complex

2016 ◽  
Vol 110 (3) ◽  
pp. 358a
Author(s):  
Ali Ghavami ◽  
Liesbeth M. Veenhoff ◽  
Erik Van der Giessen ◽  
Patrick R. Onck
Keyword(s):  
Nuclear Pore Complex ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Intrinsically Disordered

scholarly journals DNA origami scaffold for studying intrinsically disordered proteins of the nuclear pore complex

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Philip Ketterer ◽  
Adithya N. Ananth ◽  
Diederik S. Laman Trip ◽  
Ankur Mishra ◽  
Eva Bertosin ◽  
...  
Keyword(s):  
Nuclear Pore Complex ◽  
Intrinsically Disordered Proteins ◽  
Dna Origami ◽  
Disordered Proteins ◽  
Nuclear Pore ◽  
Intrinsically Disordered
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