Simulations of nuclear pore transport yield mechanistic insights and quantitative predictions
Joshua S. Mincer a,b and Sanford M. Simon a,1
Author Affiliations
aLaboratory of Cellular Biophysics, Rockefeller University, 1230 York Avenue, New York, NY 10065; and
bDepartment of Anesthesiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029
Edited by Charles S. Peskin, New York University, New York, NY, and approved May 16, 2011 (received for review March 24, 2011)
Abstract
To study transport through the nuclear pore complex, we developed a computational simulation that is based on known structural elements rather than a particular transport model. Results agree with a variety of experimental data including size cutoff for cargo transport with (30-nm diameter) and without (< 10 nm) nuclear localization signals (NLS), macroscopic transport rates (hundreds per second), and single cargo transit times (milliseconds). The recently observed bimodal cargo distribution is predicted, as is the relative invariance of single cargo transit times out to large size (even as macroscopic transport rate decreases). Additional predictions concern the effects of the number of NLS tags, the RanGTP gradient, and phenylalanine-glycine nucleopore protein (FG-Nup) structure, flexibility, and cross-linking. Results are consistent with and elucidate the molecular mechanisms of some existing hypotheses (selective phase, virtual gate, and selective gate models). A model emerges that is a hybrid of a number of preexisting models as well as a Brownian ratchet model, in which a cargo-karyopherin complex remains bound to the same FG-Nups for its entire trajectory through the nuclear pore complex until RanGTP severs the cargo-Nup bonds to effect release into the nucleus.
Footnotes
↵1To whom correspondence should be addressed.
E-mail:simon@rockefeller.edu.
Author contributions: J.S.M. and S.M.S. designed research; J.S.M. and S.M.S. performed research; J.S.M. contributed new reagents/analytic tools; J.S.M. and S.M.S. analyzed data; and J.S.M. and S.M.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at
+++++
