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

• Published in: Biophysical journal Vol. 116; no. 7; pp. 1204 - 1215
• Main Authors: Gu, Chad, Vovk, Andrei, Zheng, Tiantian, Coalson, Rob D., Zilman, Anton
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.04.2019; The Biophysical Society
• 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
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/j.bpj.2019.02.028

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.