IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v3y2012i1d10.1038_ncomms2126.html
   My bibliography  Save this article

Structural and molecular insights into the mechanism of action of human angiogenin-ALS variants in neurons

Author

Listed:
  • Nethaji Thiyagarajan

    (University of Bath, Claverton Down)

  • Ross Ferguson

    (University of Bath, Claverton Down)

  • Vasanta Subramanian

    (University of Bath, Claverton Down)

  • K. Ravi Acharya

    (University of Bath, Claverton Down)

Abstract

Mutations in angiogenin (ANG), a member of the ribonuclease A superfamily, are associated with amyotrophic lateral sclerosis (ALS; sporadic and familial) and Parkinson's disease. We have previously shown that ANG is expressed in neurons during neuro-ectodermal differentiation, and that it has both neurotrophic and neuroprotective functions. Here we report the atomic resolution structure of native ANG and 11 ANG-ALS variants. We correlate the structural changes to the effects on neuronal survival and the ability to induce stress granules in neuronal cell lines. ANG-ALS variants that affect the structure of the catalytic site and either decrease or increase the RNase activity affect neuronal survival. Neuronal cell lines expressing the ANG-ALS variants also lack the ability to form stress granules. Our structure–function studies on these ANG-ALS variants are the first to provide insights into the cellular and molecular mechanisms underlying their role in ALS.

Suggested Citation

  • Nethaji Thiyagarajan & Ross Ferguson & Vasanta Subramanian & K. Ravi Acharya, 2012. "Structural and molecular insights into the mechanism of action of human angiogenin-ALS variants in neurons," Nature Communications, Nature, vol. 3(1), pages 1-14, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2126
    DOI: 10.1038/ncomms2126
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms2126
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms2126?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
    ---><---

    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:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2126. 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.