{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ullrich T"],"funding":["Deutsche Forschungsgemeinschaft","José Carreras Leukämie-Stiftung","M. Schickedanz Kinderkrebsstiftung","Max-Planck-Gesellschaft"],"pagination":["e3002883"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11596305"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["22(11)"],"pubmed_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 human hematopoietic stem cells. Thus, the"],"journal":["PLoS biology"],"pubmed_title":["A strategy to design protein-based antagonists against type I cytokine receptors."],"pmcid":["PMC11596305"],"funding_grant_id":["500215849","DJCLS 10 R/2024","PI 405/15"],"pubmed_authors":["Skokowa J","Lasram A","Piehler J","Milijas-Jotic M","Ullrich T","Hatskovska V","Schenk L","ElGamacy M","Klimenkova O","Pollmann C","Maksymenko K","Hartmann MD","Lengerke C"],"additional_accession":[]},"is_claimable":false,"name":"A strategy to design protein-based antagonists against type I cytokine receptors.","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 human hematopoietic stem cells. Thus, the","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-06-01T06:43:44.2Z","creation":"2025-04-04T00:45:20.503Z"},"accession":"S-EPMC11596305","cross_references":{"pubmed":["39591631"],"doi":["10.1371/journal.pbio.3002883"]}}