Nanocompartmentalization of the Nuclear Pore Lumen

Kai Huang, Mario Tagliazucchi, Sung Hyun Park, Yitzhak Rabin, Igal Szleifer

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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 languageEnglish
Pages (from-to)219-231
Number of pages13
JournalBiophysical Journal
Issue number1
StatePublished - 7 Jan 2020

Bibliographical note

Funding Information:
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 .

Publisher Copyright:
© 2019 Biophysical Society


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