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Part 1: Document Description
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Citation |
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Title: |
A Strategy to Design Protein-based Antagonists Against Type I Cytokine Receptors |
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Identification Number: |
doi:10.26249/FK2/NPX7DU |
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Distributor: |
osnaData |
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Date of Distribution: |
2024-08-30 |
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Version: |
1 |
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Bibliographic Citation: |
Pollmann, Christoph, 2024, "A Strategy to Design Protein-based Antagonists Against Type I Cytokine Receptors", https://doi.org/10.26249/FK2/NPX7DU, osnaData, V1 |
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Citation |
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Title: |
A Strategy to Design Protein-based Antagonists Against Type I Cytokine Receptors |
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Identification Number: |
doi:10.26249/FK2/NPX7DU |
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Authoring Entity: |
Pollmann, Christoph (Osnabrück University) |
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Distributor: |
osnaData |
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Access Authority: |
Pollmann, Christoph |
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Depositor: |
Pollmann, Christoph |
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Date of Deposit: |
2024-08-30 |
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Study Scope |
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Keywords: |
Medicine, Health and Life Sciences |
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Abstract: |
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. |
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CC0 Waiver |
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Other Study Description Materials |
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Related Publications |
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Citation |
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Bibliographic Citation: |
Link to raw data: https://omero.cellnanos.uni-osnabrueck.de/webclient/?show=project-15707 |