Natively unfolded nucleoporins gate protein diffusion across the nuclear pore complex

Area of Science:

• Cell Biology
• Molecular Biology
• Biophysics

Background:

• Nuclear pore complexes (NPCs) regulate transport between the nucleus and cytoplasm.
• Nucleoporins with phenylalanine-glycine (FG) motifs are key to NPC function but their precise role in selectivity is debated.

Purpose of the Study:

• To investigate the role of FG domains in the NPC's size-selective barrier.
• To elucidate the structural organization and interactions of FG domains within the NPC.

Main Methods:

• Yeast genetics to delete individual FG domains.
• Analysis of NPC permeability changes upon FG domain deletion.
• Biochemical assays to study FG domain interactions and their disruption by alcohols.

Main Results:

• Deletion of individual FG domains compromises the NPC's permeability barrier.
• Central FG domains form a cohesive, hydrophobic meshwork via FG motifs, disrupted by alcohols.
• Peripheral FG domains are generally noncohesive.

Conclusions:

• The NPC operates via a two-gate model.
• A central diffusion gate is formed by cohesive FG nucleoporin filaments.
• A peripheral gate is formed by noncohesive FG nucleoporin filaments.