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: 2024-11-20)

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

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: 37339051
DOI: 10.1016/j.celrep.2023.112657

Experimental method

X-RAY DIFFRACTION (2.83 Å)