The Role of Cohesiveness in the Permeability of the Spatial Assemblies of FG Nucleoporins

Nuclear pore complexes (NPCs) conduct selective, bidirectional transport across the nuclear envelope. The NPC passageway is lined by intrinsically disordered proteins that contain hydrophobic phenylalanine-glycine (FG) motifs, known as FG nucleoporins (FG nups), that play the key role in the NPC tra...

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Bibliographic Details
Published in:Biophysical journal 2019-04, Vol.116 (7), p.1204-1215
Main Authors: Gu, Chad, Vovk, Andrei, Zheng, Tiantian, Coalson, Rob D., Zilman, Anton
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus
Computer Simulation
Glycine - chemistry
Nuclear Pore - chemistry
Nuclear Pore - metabolism
Nuclear Pore Complex Proteins - chemistry
Nuclear Pore Complex Proteins - metabolism
Phenylalanine - chemistry
Protein Multimerization
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Summary:Nuclear pore complexes (NPCs) conduct selective, bidirectional transport across the nuclear envelope. The NPC passageway is lined by intrinsically disordered proteins that contain hydrophobic phenylalanine-glycine (FG) motifs, known as FG nucleoporins (FG nups), that play the key role in the NPC transport mechanism. Cohesive interactions among the FG nups, which arise from the combination of hydrophobic, electrostatic, and other forces, have been hypothesized to control the morphology of the assemblies of FG nups in the NPC, as well as their permeability with respect to the transport proteins. However, the role of FG nup cohesiveness is still vigorously debated. Using coarse-grained polymer theory and numerical simulations, we study the effects of cohesiveness on the selective permeability of in vitro FG nup assemblies in different geometries that have served as proxies for the morphological and transport properties of the NPC. We show that in high-density FG nup assemblies, increase in cohesiveness leads to the decrease in their permeability, in accordance with the accepted view. On the other hand, the permeability of low-density assemblies is a nonmonotonic function of the cohesiveness, and a moderate increase in cohesiveness can enhance permeability. The density- and cohesiveness-dependent effects on permeability are explained by considering the free-energy cost associated with penetrating the FG nup assemblies. We discuss the implications of these findings for the organization and function of the NPC.
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2019.02.028