1. Structural Biology and Molecular Biophysics
  2. Cell Biology
Download icon

A tethered delivery mechanism explains the catalytic action of a microtubule polymerase

Research Article
  • Cited 51
  • Views 2,254
  • Annotations
Cite this article as: eLife 2014;3:e03069 doi: 10.7554/eLife.03069

Abstract

Stu2p/XMAP215 proteins are essential microtubule polymerases that use multiple αβ-tubulin-interacting TOG domains to bind microtubule plus ends and catalyze fast microtubule growth. We report here the structure of the TOG2 domain from Stu2p bound to yeast αβ-tubulin. Like TOG1, TOG2 binds selectively to a fully 'curved' conformation of αβ-tubulin, incompatible with a microtubule lattice. We also show that TOG1-TOG2 binds non-cooperatively to two αβ-tubulins. Preferential interactions between TOGs and fully curved αβ-tubulin that cannot exist elsewhere in the microtubule explain how these polymerases localize to the extreme microtubule end. We propose that these polymerases promote elongation because their linked TOG domains concentrate unpolymerized αβ-tubulin near curved subunits already bound at the microtubule end. This tethering model can explain catalyst-like behavior and also predicts that the polymerase action changes the configuration of the microtubule end.

Article and author information

Author details

  1. Pelin Ayaz

    UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sarah Munyoki

    UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Elisabeth A Geyer

    UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Felipe-Andrés Piedra

    UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Emily S Vu

    UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Raquel Bromberg

    UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Zbyszek Otwinowski

    UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Nick V Grishin

    UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Chad A Brautigam

    UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Luke M Rice

    UT Southwestern Medical Center, Dallas, United States
    For correspondence
    Luke.Rice@UTSouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Stephen C Harrison, Harvard Medical School, United States

Publication history

  1. Received: April 11, 2014
  2. Accepted: August 4, 2014
  3. Accepted Manuscript published: August 5, 2014 (version 1)
  4. Version of Record published: August 29, 2014 (version 2)

Copyright

© 2014, Ayaz 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.

Metrics

  • 2,254
    Page views
  • 296
    Downloads
  • 51
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Structural Biology and Molecular Biophysics
    Lan Wang et al.
    Research Article Updated
    1. Structural Biology and Molecular Biophysics
    Björn Udo Klink et al.
    Research Article Updated