Nanocompartmentalization of the Nuclear Pore Lumen

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

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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 languageEnglish
Pages (from-to)219-231
Number of pages13
JournalBiophysical Journal
Volume118
Issue number1
DOIs
StatePublished - 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 .

FundersFunder number
National Science Foundation1833214
National Institutes of Health
National Cancer InstituteR01CA228272
Israel Science Foundation1902/12, 178/16

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