Simple rules for passive diffusion through the nuclear pore complex.

Passive macromolecular diffusion through nuclear pore complexes (NPCs) is thought to decrease dramatically beyond a 30-60-kD size threshold. Using thousands of independent time-resolved fluorescence microscopy measurements in vivo, we show that the NPC lacks such a firm size threshold; instead, it forms a soft barrier to passive diffusion that intensifies gradually with increasing molecular mass in both the wild-type and mutant strains with various subsets of phenylalanine-glycine (FG) domains and different levels of baseline passive permeability. Brownian dynamics simulations replicate these findings and indicate that the soft barrier results from the highly dynamic FG repeat domains and the diffusing macromolecules mutually constraining and competing for available volume in the interior of the NPC, setting up entropic repulsion forces. We found that FG domains with exceptionally high net charge and low hydropathy near the cytoplasmic end of the central channel contribute more strongly to obstruction of passive diffusion than to facilitated transport, revealing a compartmentalized functional arrangement within the NPC

Integrative structure and functional anatomy of a nuclear pore complex

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Simple rules for passive diffusion through the nuclear pore complex

Passive macromolecular diffusion through nuclear pore complexes (NPCs) is thought to decrease dramatically beyond a 30–60-kD size threshold. Using thousands of independent time-resolved fluorescence microscopy measurements in vivo, we show that the NPC lacks such a firm size threshold; instead, it forms a soft barrier to passive diffusion that intensifies gradually with increasing molecular mass in both the wild-type and mutant strains with various subsets of phenylalanine-glycine (FG) domains and different levels of baseline passive permeability. Brownian dynamics simulations replicate these findings and indicate that the soft barrier results from the highly dynamic FG repeat domains and the diffusing macromolecules mutually constraining and competing for available volume in the interior of the NPC, setting up entropic repulsion forces. We found that FG domains with exceptionally high net charge and low hydropathy near the cytoplasmic end of the central channel contribute more strongly to obstruction of passive diffusion than to facilitated transport, revealing a compartmentalized functional arrangement within the NPC

Brownian Dynamics simulations of yeast Nuclear Pore Complex FG repeats

<p>The files in this folder can be used to reproduce the Brownian Dynamics simulations of FG repeats using IMP as described in Kim et al., 2018.</p

Modeling of the yeast Nuclear Pore Complex

<p>These scripts demonstrate the use of <a href="http://salilab.org/imp">IMP</a> in the modeling of the yeast NPC complex using diverse types of data as described in Seung Joong Kim, et al.'s 2018 NPC article published in Nature.</p> <p><strong>For more information</strong> about how to reproduce this modeling, see the <a href="https://salilab.org/npc2018/">Sali lab website</a> or the README file.</p