IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v411y2001i6834d10.1038_35075620.html
   My bibliography  Save this article

The structural basis of Arfaptin-mediated cross-talk between Rac and Arf signalling pathways

Author

Listed:
  • C. Tarricone

    (National Institute for Medical Research
    European Institute of Oncology)

  • B. Xiao

    (National Institute for Medical Research)

  • N. Justin

    (National Institute for Medical Research)

  • P. A. Walker

    (National Institute for Medical Research)

  • K. Rittinger

    (National Institute for Medical Research)

  • S. J. Gamblin

    (National Institute for Medical Research)

  • S. J. Smerdon

    (National Institute for Medical Research)

Abstract

Small G proteins are GTP-dependent molecular switches that regulate numerous cellular functions1. They can be classified into homologous subfamilies that are broadly associated with specific biological processes. Cross-talk between small G-protein families has an important role in signalling, but the mechanism by which it occurs is poorly understood2. The coordinated action of Arf and Rho family GTPases is required to regulate many cellular processes including lipid signalling3, cell motility4 and Golgi function5. Arfaptin is a ubiquitously expressed protein implicated in mediating cross-talk between Rac (a member of the Rho family) and Arf small GTPases. Here we show that Arfaptin binds specifically to GTP-bound Arf1 and Arf6, but binds to Rac·GTP and Rac·GDP with similar affinities. The X-ray structure of Arfaptin reveals an elongated, crescent-shaped dimer of three-helix coiled-coils. Structures of Arfaptin with Rac bound to either GDP or the slowly hydrolysable analogue GMPPNP show that the switch regions adopt similar conformations in both complexes. Our data highlight fundamental differences between the molecular mechanisms of Rho and Ras family signalling, and suggest a model of Arfaptin-mediated synergy between the Arf and Rho family signalling pathways.

Suggested Citation

  • C. Tarricone & B. Xiao & N. Justin & P. A. Walker & K. Rittinger & S. J. Gamblin & S. J. Smerdon, 2001. "The structural basis of Arfaptin-mediated cross-talk between Rac and Arf signalling pathways," Nature, Nature, vol. 411(6834), pages 215-219, May.
    • Handle: RePEc:nat:nature:v:411:y:2001:i:6834:d:10.1038_35075620
    DOI: 10.1038/35075620
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/35075620
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/35075620?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Albert Solernou & Benjamin S Hanson & Robin A Richardson & Robert Welch & Daniel J Read & Oliver G Harlen & Sarah A Harris, 2018. "Fluctuating Finite Element Analysis (FFEA): A continuum mechanics software tool for mesoscale simulation of biomolecules," PLOS Computational Biology, Public Library of Science, vol. 14(3), pages 1-29, March.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:411:y:2001:i:6834:d:10.1038_35075620. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.