Probing a structural model of the nuclear pore complex channel through molecular dynamics

Area of Science:

• Biophysics
• Cell Biology
• Molecular Biology

Background:

• Nuclear pore complexes (NPCs) regulate transport between the nucleus and cytoplasm.
• FG-repeat proteins within the NPC central channel are crucial for selective transport.
• Previous simulations suggested a brushlike structure formed by nsp1 segments.

Purpose of the Study:

• To investigate the interaction of the FG-repeat brush structure with transport receptor NTF2 and an inert protein.
• To understand the mechanism of selective transport through the NPC channel.
• To evaluate the role of FG-repeat binding in selective transport.

Main Methods:

• Four molecular dynamics simulations were performed with 350,000 atoms over 200 ns.
• The simulations probed the interaction of an nsp1 FG-repeat brush with NTF2 dimers and an inert protein.
• A simulation also tested a brush made of mutant nsp1.

Main Results:

• NTF2 dimers gradually entered the FG-repeat brush, while the inert protein did not.
• Both NTF2 and the inert protein bound to FG-repeats, but inert protein binding was transient.
• A mutant nsp1 brush, known for reduced NPC transport efficiency, failed to attract NTF2.

Conclusions:

• The FG-repeat brush structure facilitates the selective entry of transport receptors like NTF2.
• Differential binding dynamics to FG-repeats underlie the selectivity of the NPC.
• Mutations affecting FG-repeat structure or properties impair selective transport, confirming the brush model's validity.