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基本情報
登録情報 | データベース: PDB / ID: 8ent | |||||||||
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タイトル | Interleukin-21 signaling complex with IL-21R and IL-2Rg | |||||||||
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![]() | CYTOKINE/CYTOKINE RECEPTOR / IL-21 / receptor / complex / signaling / CYTOKINE / CYTOKINE-CYTOKINE RECEPTOR complex | |||||||||
機能・相同性 | ![]() interleukin-21 receptor activity / mature B cell differentiation / interleukin-15 receptor activity / interleukin-2 binding / CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / interleukin-2 receptor binding / tyrosine phosphorylation of STAT protein / germinal center B cell differentiation / positive regulation of tissue remodeling / positive regulation of T cell differentiation in thymus ...interleukin-21 receptor activity / mature B cell differentiation / interleukin-15 receptor activity / interleukin-2 binding / CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / interleukin-2 receptor binding / tyrosine phosphorylation of STAT protein / germinal center B cell differentiation / positive regulation of tissue remodeling / positive regulation of T cell differentiation in thymus / lymphocyte differentiation / Interleukin-9 signaling / Interleukin-21 signaling / interleukin-7-mediated signaling pathway / interleukin-9-mediated signaling pathway / interleukin-4-mediated signaling pathway / positive regulation of natural killer cell mediated cytotoxicity / positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation / interleukin-2-mediated signaling pathway / cytokine receptor binding / T follicular helper cell differentiation / interleukin-15-mediated signaling pathway / cellular homeostasis / STAT3 nuclear events downstream of ALK signaling / Interleukin-15 signaling / cytokine receptor activity / natural killer cell activation / Interleukin-2 signaling / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of B cell differentiation / positive regulation of immunoglobulin production / cytokine binding / positive regulation of interleukin-17 production / Interleukin receptor SHC signaling / cell maturation / coreceptor activity / positive regulation of phagocytosis / positive regulation of B cell proliferation / positive regulation of T cell proliferation / Interleukin-7 signaling / positive regulation of cytokine production / cytokine activity / cytokine-mediated signaling pathway / cellular response to virus / positive regulation of type II interferon production / positive regulation of inflammatory response / transmembrane signaling receptor activity / T cell differentiation in thymus / RAF/MAP kinase cascade / Interleukin-4 and Interleukin-13 signaling / defense response to virus / gene expression / receptor complex / endosome / immune response / external side of plasma membrane / positive regulation of cell population proliferation / cell surface / signal transduction / extracellular space / extracellular region / nucleoplasm / membrane / plasma membrane / cytosol 類似検索 - 分子機能 | |||||||||
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![]() | Abhiraman, G.C. / Jude, K.M. / Garcia, K.C. | |||||||||
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![]() | ![]() タイトル: A structural blueprint for interleukin-21 signal modulation. 著者: Gita C Abhiraman / Theodora U J Bruun / Nathanael A Caveney / Leon L Su / Robert A Saxton / Qian Yin / Shaogeng Tang / Mark M Davis / Kevin M Jude / K Christopher Garcia / ![]() 要旨: 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 ...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. | |||||||||
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