Ramya Gamini, Wei Han, John E. Stone, and Klaus Schulten.
Assembly of Nsp1 nucleoporins provides insight into nuclear pore
complex gating.
PLoS Computational Biology, 10:e1003488, 2014.
(14 pages).
(PMC: PMC3952814)
GAMI2014
Nuclear pore complexes (NPCs) are gateways for passage of material across the
nuclear envelope of eukaryotic cells. Several unstructured proteins, rich in phenylaline-
glycine motifs (FG-nups), form the central transport channel. Small molecules passively
diffuse through, but larger molecules need transport factors, that pass apparently by
means of interaction with the FG-repeats of the nups in the channel. Understanding how
nups are arranged in the interior of the NPC may explain why large molecules pass only
when assisted by transport factors. We employed coarse-grained molecular dynamics
simulations to simulate the structures formed by various assemblies of one kind of nup,
namely the 609-aa-long Nsp1. The simulations started from different initial
conformations and geometrical arrangements of Nsp1s. In all cases Nsp1s collectively
formed brush-like structures with bristles made of bundles of 2-27 nups, however, the
bundles being cross-linked through single nups leaving one bundle and joining a nearby
one. The degree of cross-linking varies with different initial nup conformations and
arrangements. The structures formed are independent of FG-repeats, indicating that FGs
act only as interaction sites for transport factors, but are not structural determinants of the
NPC pore interior. The simulations suggest then that the NPC central channel, near the
periphery where tethering of nups is dominant, features brush-like moderately cross-
linked bundles, but in the central region, where tethering looses its effect, features a
sieve-like structure of bundles and frequent cross-links. The cross-linking between Nsp1
bundles simulated is found to set a molecular size limit of 9 nm for passive
diffusion of molecules. Larger biomolecules need to bind to transport factors to pass
through nuclear pores; the transport factors must have the ability to melt the cross-linking
between nups bundles creating, thereby, wide enough space for themselves and their
cargoes to pass.
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