IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-13343-7.html
   My bibliography  Save this article

Crystal structure and receptor-interacting residues of MYDGF — a protein mediating ischemic tissue repair

Author

Listed:
  • Rebecca Ebenhoch

    (Boehringer Ingelheim Pharma GmbH & Co. KG)

  • Abbas Akhdar

    (Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School)

  • Marc R. Reboll

    (Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School)

  • Mortimer Korf-Klingebiel

    (Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School)

  • Priyanka Gupta

    (Boehringer Ingelheim Pharmaceuticals, Inc.)

  • Julie Armstrong

    (Boehringer Ingelheim Pharmaceuticals, Inc.)

  • Yining Huang

    (Boehringer Ingelheim Pharmaceuticals, Inc.)

  • Lee Frego

    (Boehringer Ingelheim Pharmaceuticals, Inc.)

  • Irina Rybina

    (Boehringer Ingelheim Pharmaceuticals, Inc.)

  • John Miglietta

    (Boehringer Ingelheim Pharmaceuticals, Inc.)

  • Anton Pekcec

    (Boehringer Ingelheim Pharma GmbH & Co. KG)

  • Kai C. Wollert

    (Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School)

  • Herbert Nar

    (Boehringer Ingelheim Pharma GmbH & Co. KG)

Abstract

Myeloid-derived growth factor (MYDGF) is a paracrine-acting protein that is produced by bone marrow-derived monocytes and macrophages to protect and repair the heart after myocardial infarction (MI). This effect can be used for the development of protein-based therapies for ischemic tissue repair, also beyond the sole application in heart tissue. Here, we report the X-ray structure of MYDGF and identify its functionally relevant receptor binding epitope. MYDGF consists of a 10-stranded β-sandwich with a folding topology showing no similarities to other cytokines or growth factors. By characterizing the epitope of a neutralizing antibody and utilizing functional assays to study the activity of surface patch-mutations, we were able to localize the receptor interaction interface to a region around two surface tyrosine residues 71 and 73 and an adjacent prominent loop structure of residues 97–101. These findings enable structure-guided protein engineering to develop modified MYDGF variants with potentially improved properties for clinical use.

Suggested Citation

  • Rebecca Ebenhoch & Abbas Akhdar & Marc R. Reboll & Mortimer Korf-Klingebiel & Priyanka Gupta & Julie Armstrong & Yining Huang & Lee Frego & Irina Rybina & John Miglietta & Anton Pekcec & Kai C. Woller, 2019. "Crystal structure and receptor-interacting residues of MYDGF — a protein mediating ischemic tissue repair," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13343-7
    DOI: 10.1038/s41467-019-13343-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-13343-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-019-13343-7?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
    ---><---

    Citations

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


    Cited by:

    1. Linda Große-Segerath & Paula Follert & Kristina Behnke & Julia Ettich & Tobias Buschmann & Philip Kirschner & Sonja Hartwig & Stefan Lehr & Mortimer Korf-Klingebiel & Daniel Eberhard & Nadja Lehwald-T, 2024. "Identification of myeloid-derived growth factor as a mechanically-induced, growth-promoting angiocrine signal for human hepatocytes," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    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:10:y:2019:i:1:d:10.1038_s41467-019-13343-7. 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.