{"@context":"http://schema.org","@type":"Dataset","@id":"https://doi.org/10.26249/FK2/NPX7DU","identifier":"https://doi.org/10.26249/FK2/NPX7DU","name":"A Strategy to Design Protein-based Antagonists Against Type I Cytokine Receptors","creator":[{"name":"Pollmann, Christoph","affiliation":"Osnabrück University","@id":"https://orcid.org/0000-0002-1473-0288","identifier":"https://orcid.org/0000-0002-1473-0288"}],"author":[{"name":"Pollmann, Christoph","affiliation":"Osnabrück University","@id":"https://orcid.org/0000-0002-1473-0288","identifier":"https://orcid.org/0000-0002-1473-0288"}],"datePublished":"2024-08-30","dateModified":"2024-08-30","version":"1","description":["Excessive cytokine signaling resulting from dysregulation of a cytokine or its receptor can be a main driver of cancer, autoimmune or hematopoietic disorders. Here we leverage protein design to create tailored cytokine receptor blockers with idealized properties. Specifically, we aimed to tackle the granulocyte-colony stimulating factor receptor (G-CSFR), a mediator of different types of leukemia and autoinflammatory diseases. By modifying designed G-CSFR binders, we engineered hyper-stable proteins that function as nanomolar signaling antagonists. X-ray crystallography showed atomic-level agreement with the experimental structure of an exemplary design. Furthermore, the most potent design blocks G-CSFR in acute myeloid leukemia cells and primary hematopoietic stem cells. Thus, the resulting designs can be used for inhibiting or homing to G-CSFR-expressing cells. Our work also demonstrates that designed cytokine mimics can be used to derive non-activating variants for tackling a range of cytokine receptors."],"keywords":["Medicine, Health and Life Sciences"],"citation":[{"@type":"CreativeWork","text":"Link to raw data: https://omero.cellnanos.uni-osnabrueck.de/webclient/?show=project-15707","@id":"https://omero.cellnanos.uni-osnabrueck.de/webclient/?show=project-15707","identifier":"https://omero.cellnanos.uni-osnabrueck.de/webclient/?show=project-15707"}],"license":{"@type":"Dataset","text":"CC0","url":"https://creativecommons.org/publicdomain/zero/1.0/"},"includedInDataCatalog":{"@type":"DataCatalog","name":"osnaData","url":"https://osnadata.ub.uni-osnabrueck.de"},"publisher":{"@type":"Organization","name":"osnaData"},"provider":{"@type":"Organization","name":"osnaData"}}