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TitleStructure of the interleukin-5 receptor complex exemplifies the organizing principle of common beta cytokine signaling.
Journal, issue, pagesMol Cell, Vol. 84, Issue 10, Page 1995-12005.e7, Year 2024
Publish dateMay 16, 2024
AuthorsNathanael A Caveney / Grayson E Rodriguez / Christoph Pollmann / Thomas Meyer / Marta T Borowska / Steven C Wilson / Nan Wang / Xinyu Xiang / Karsten D Householder / Pingdong Tao / Leon L Su / Robert A Saxton / Jacob Piehler / K Christopher Garcia /
PubMed AbstractCytokines regulate immune responses by binding to cell surface receptors, including the common subunit beta (βc), which mediates signaling for GM-CSF, IL-3, and IL-5. Despite known roles in ...Cytokines regulate immune responses by binding to cell surface receptors, including the common subunit beta (βc), which mediates signaling for GM-CSF, IL-3, and IL-5. Despite known roles in inflammation, the structural basis of IL-5 receptor activation remains unclear. We present the cryo-EM structure of the human IL-5 ternary receptor complex, revealing architectural principles for IL-5, GM-CSF, and IL-3. In mammalian cell culture, single-molecule imaging confirms hexameric IL-5 complex formation on cell surfaces. Engineered chimeric receptors show that IL-5 signaling, as well as IL-3 and GM-CSF, can occur through receptor heterodimerization, obviating the need for higher-order assemblies of βc dimers. These findings provide insights into IL-5 and βc receptor family signaling mechanisms, aiding in the development of therapies for diseases involving deranged βc signaling.
External linksMol Cell / PubMed:38614096 / PubMed Central
MethodsEM (single particle)
Resolution3.6 - 3.8 Å
Structure data

41367

8tld

EMDB-41367, PDB-8tld:
Structure of the IL-5 Signaling Complex
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-41368: GM-CSF Receptor Complex
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-41369: IL-3 Receptor Complex
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
KeywordsSIGNALING PROTEIN / IL-5 / cytokine / receptor

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