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Title: A coarse-grained computational model of the nuclear pore complex predicts Phe-Gly nucleoporin dynamics

The phenylalanine-glycine–repeat nucleoporins (FG-Nups), which occupy the lumen of the nuclear pore complex (NPC), are critical for transport between the nucleus and cytosol. Although NPCs differ in composition across species, they are largely conserved in organization and function. Transport through the pore is on the millisecond timescale. Here, to explore the dynamics of nucleoporins on this timescale, we use coarse-grained computational simulations. These simulations generate predictions that can be experimentally tested to distinguish between proposed mechanisms of transport. Our model reflects the conserved structure of the NPC, in which FG-Nup filaments extend into the lumen and anchor along the interior of the channel. The lengths of the filaments in our model are based on the known characteristics of yeast FG-Nups. The FG-repeat sites also bind to each other, and we vary this association over several orders of magnitude and run 100-ms simulations for each value. The autocorrelation functions of the orientation of the simulated FG-Nups are compared with in vivo anisotropy data. We observe that FG-Nups reptate back and forth through the NPC at timescales commensurate with experimental measurements of the speed of cargo transport through the NPC. Our results are consistent with models of transport where FG-Nup filaments aremore » free to move across the central channel of the NPC, possibly informing how cargo might transverse the NPC.« less
Authors:
ORCiD logo ; ; ORCiD logo ; ORCiD logo ; ORCiD logo
Publication Date:
Grant/Contract Number:
DEFG0288ER25053
Type:
Published Article
Journal Name:
Journal of General Physiology
Additional Journal Information:
Journal Volume: 149; Journal Issue: 10; Related Information: CHORUS Timestamp: 2018-03-13 18:07:07; Journal ID: ISSN 0022-1295
Publisher:
Rockefeller University Press
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
OSTI Identifier:
1380055