The molecular mechanism of nuclear transport revealed by atomic-scale measurements

Loren E. Hough, Kaushik Dutta, Samuel Sparks, Deniz B. Temel, Alia Kamal, Jaclyn Tetenbaum-Novatt, Michael P. Rout, David Cowburn

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Nuclear pore complexes (NPCs) form a selective filter that allows the rapid passage of transport factors (TFs) and their cargoes across the nuclear envelope, while blocking the passage of other macromolecules. Intrinsically disordered proteins (IDPs) containing phenylalanyl-glycyl (FG)-rich repeats line the pore and interact with TFs. However, the reason that transport can be both fast and specific remains undetermined, through lack of atomic-scale information on the behavior of FGs and their interaction with TFs. We used nuclear magnetic resonance spectroscopy to address these issues. We show that FG repeats are highly dynamic IDPs, stabilized by the cellular environment. Fast transport of TFs is supported because the rapid motion of FG motifs allows them to exchange on and off TFs extremely quickly through transient interactions. Because TFs uniquely carry multiple pockets for FG repeats, only they can form the many frequent interactions needed for specific passage between FG repeats to cross the NPC.

Original languageEnglish (US)
Article numbere10027
JournaleLife
Volume4
Issue numberSeptember
DOIs
StatePublished - Sep 15 2015

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Hough, L. E., Dutta, K., Sparks, S., Temel, D. B., Kamal, A., Tetenbaum-Novatt, J., Rout, M. P., & Cowburn, D. (2015). The molecular mechanism of nuclear transport revealed by atomic-scale measurements. eLife, 4(September), [e10027]. https://doi.org/10.7554/eLife.10027