8TLD

Structure of the IL-5 Signaling Complex

Summary for 8TLD

• Entry DOI: 10.2210/pdb8tld/pdb
• EMDB information: 41367
• Descriptor: Cytokine receptor common subunit beta, Interleukin-5, Interleukin-5 receptor subunit alpha, ... (4 entities in total)
• Functional Keywords: il-5, cytokine, receptor, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 241525.82

Authors

Caveney, N.A.,Garcia, K.C. (deposition date: 2023-07-26, release date: 2024-04-10, Last modification date: 2024-12-11)

Primary citation

Caveney, N.A.,Rodriguez, G.E.,Pollmann, C.,Meyer, T.,Borowska, M.T.,Wilson, S.C.,Wang, N.,Xiang, X.,Householder, K.D.,Tao, P.,Su, L.L.,Saxton, R.A.,Piehler, J.,Garcia, K.C.
Structure of the interleukin-5 receptor complex exemplifies the organizing principle of common beta cytokine signaling.
Mol.Cell, 84:1995-2005.e7, 2024

PubMed Abstract: 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.

PubMed: 38614096
DOI: 10.1016/j.molcel.2024.03.023

Experimental method

ELECTRON MICROSCOPY (3.6 Å)