8ent | pdb_00008ent
Interleukin-21 signaling complex with IL-21R and IL-2Rg
Structural highlights
FunctionIL21_HUMAN Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells (By similarity). May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells. During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation.[1] [2] Publication Abstract from PubMedInterleukin-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-gammac 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-gammac 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. A structural blueprint for interleukin-21 signal modulation.,Abhiraman GC, Bruun TUJ, Caveney NA, Su LL, Saxton RA, Yin Q, Tang S, Davis MM, Jude KM, Garcia KC Cell Rep. 2023 Jun 19;42(6):112657. doi: 10.1016/j.celrep.2023.112657. PMID:37339051[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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