8ENT
Interleukin-21 signaling complex with IL-21R and IL-2Rg
Summary for 8ENT
Entry DOI | 10.2210/pdb8ent/pdb |
EMDB information | 28278 |
Descriptor | Interleukin-21, Interleukin-21 receptor, Cytokine receptor common subunit gamma, ... (8 entities in total) |
Functional Keywords | il-21, receptor, complex, signaling, cytokine, cytokine-cytokine receptor complex, cytokine/cytokine receptor |
Biological source | Homo sapiens (human) More |
Total number of polymer chains | 11 |
Total formula weight | 255810.50 |
Authors | Abhiraman, G.C.,Jude, K.M.,Garcia, K.C. (deposition date: 2022-09-30, release date: 2023-06-28, Last modification date: 2023-10-25) |
Primary citation | Abhiraman, G.C.,Bruun, T.U.J.,Caveney, N.A.,Su, L.L.,Saxton, R.A.,Yin, Q.,Tang, S.,Davis, M.M.,Jude, K.M.,Garcia, K.C. A structural blueprint for interleukin-21 signal modulation. Cell Rep, 42:112657-112657, 2023 Cited by PubMed Abstract: Interleukin-21 (IL-21) plays a critical role in generating immunological memory by promoting the germinal center reaction, yet clinical use of IL-21 remains challenging because of its pleiotropy and association with autoimmune disease. To better understand the structural basis of IL-21 signaling, we determine the structure of the IL-21-IL-21R-γc ternary signaling complex by X-ray crystallography and a structure of a dimer of trimeric complexes using cryo-electron microscopy. Guided by the structure, we design analogs of IL-21 by introducing substitutions to the IL-21-γc interface. These IL-21 analogs act as partial agonists that modulate downstream activation of pS6, pSTAT3, and pSTAT1. These analogs exhibit differential activity on T and B cell subsets and modulate antibody production in human tonsil organoids. These results clarify the structural basis of IL-21 signaling and offer a potential strategy for tunable manipulation of humoral immunity. PubMed: 37339051DOI: 10.1016/j.celrep.2023.112657 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.83 Å) |
Structure validation
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