Allosteric modulation of nucleoporin assemblies by intrinsically disordered regions.

Published online

Journal Article

Intrinsically disordered regions (IDRs) of proteins are implicated in key macromolecular interactions. However, the molecular forces underlying IDR function within multicomponent assemblies remain elusive. By combining thermodynamic and structural data, we have discovered an allostery-based mechanism regulating the soluble core region of the nuclear pore complex (NPC) composed of nucleoporins Nup53, Nic96, and Nup157. We have identified distinct IDRs in Nup53 that are functionally coupled when binding to partner nucleoporins and karyopherins (Kaps) involved in NPC assembly and nucleocytoplasmic transport. We show that the Nup53·Kap121 complex forms an ensemble of structures that destabilize Nup53 hub interactions. Our study provides a molecular framework for understanding how disordered and folded domains communicate within macromolecular complexes.

Full Text

Duke Authors

Cited Authors

  • Blus, BJ; Koh, J; Krolak, A; Seo, H-S; Coutavas, E; Blobel, G

Published Date

  • November 2019

Published In

Volume / Issue

  • 5 / 11

Start / End Page

  • eaax1836 -

PubMed ID

  • 31807700

Pubmed Central ID

  • 31807700

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.aax1836

Language

  • eng

Conference Location

  • United States