The molecular mechanism of nuclear transport revealed by atomic scale measurements

  1. Loren E Hough
  2. Kaushik Dutta
  3. Samuel Sparks
  4. Deniz B Temel
  5. Alia Kamal
  6. Jaclyn Tetenbaum-Novatt
  7. Michael P Rout
  8. David Cowburn  Is a corresponding author
  1. The Rockefeller University, United States
  2. New York Structural Biology Center, United States
  3. Albert Einstein College of Medicine, United States

Abstract

Nuclear pore complexes 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 NMR 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.

Article and author information

Author details

  1. Loren E Hough

    The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Kaushik Dutta

    New York Structural Biology Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Samuel Sparks

    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Deniz B Temel

    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Alia Kamal

    The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jaclyn Tetenbaum-Novatt

    The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael P Rout

    Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. David Cowburn

    Department of Biochemistry, Albert Einstein College of Medicine, The Bronx, United States
    For correspondence
    cowburn@cowburnlab.org
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Publication history

  1. Received: July 11, 2015
  2. Accepted: September 7, 2015
  3. Accepted Manuscript published: September 15, 2015 (version 1)
  4. Accepted Manuscript updated: October 1, 2015 (version 2)
  5. Version of Record published: October 27, 2015 (version 3)

Copyright

© 2015, Hough et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Loren E Hough
  2. Kaushik Dutta
  3. Samuel Sparks
  4. Deniz B Temel
  5. Alia Kamal
  6. Jaclyn Tetenbaum-Novatt
  7. Michael P Rout
  8. David Cowburn
(2015)
The molecular mechanism of nuclear transport revealed by atomic scale measurements
eLife 4:e10027.
https://doi.org/10.7554/eLife.10027

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