Abstract
The nuclear pore complex (NPC) employs the intrinsically disordered regions (IDRs) from a family of phenylalanine-glycine-rich nucleoporins (FG-Nups) to control nucleocytoplasmic transport. It has been a long-standing mystery how the IDR-mediated mass exchange can be rapid yet selective. Here, we use a computational microscope to show that nanocompartmentalization of IDR subdomains leads to a remarkably elaborate gating structure as programmed by the amino acid sequences. In particular, we reveal a heterogeneous permeability barrier that combines an inner ring barrier with two vestibular condensates. Throughout the NPC, we find a polarized electrostatic potential and a diffuse thermoreversible FG network featuring mosaic FG territories with low FG-FG pairing fraction. Our theoretical anatomy of the central transporter sheds light into the sequence-structure-function relationship of the FG-Nups and provides a picture of nucleocytoplasmic mass exchange that allows a reconciliation of transport efficiency and specificity.
Original language | English |
---|---|
Pages (from-to) | 219-231 |
Number of pages | 13 |
Journal | Biophysical Journal |
Volume | 118 |
Issue number | 1 |
DOIs | |
State | Published - 7 Jan 2020 |
Bibliographical note
Publisher Copyright:© 2019 Biophysical Society
Funding
I.S. and K.H. gratefully acknowledge funding from National Science Foundation Biological and Environmental Interactions of Nanoscale Materials 1833214 and National Institutes of Health National Cancer Institute R01 CA228272 . Y.R. would like to acknowledge support by grants from the Israel Science Foundation 178/16 and from the Israeli Centers for Research Excellence program of the Planning and Budgeting Committee 1902/12 .
Funders | Funder number |
---|---|
National Science Foundation | 1833214 |
National Institutes of Health | |
National Cancer Institute | R01CA228272 |
Israel Science Foundation | 1902/12, 178/16 |