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Crystal structure of the IL-15-IL-15Ralpha complex, a cytokine-receptor unit presented in trans.

Chirifu M, Hayashi C, Nakamura T, Toma S, Shuto T, Kai H, Yamagata Y, Davis SJ, Ikemizu S
Nat Immunol 8 1001-7 (2007)
Cited: 54 times
EuropePMC logo PMID: 17643103

Abstract

Interleukin 15 (IL-15) and IL-2, which promote the survival of memory CD8(+) T cells and regulatory T cells, respectively, bind receptor complexes that share beta- and gamma-signaling subunits. Receptor specificity is provided by unique, nonsignaling alpha-subunits. Whereas IL-2 receptor-alpha (IL-2Ralpha) is expressed together in cis with the beta- and gamma-subunits on T cells and B cells, IL-15Ralpha is expressed in trans on antigen-presenting cells. Here we present a 1.85-A crystal structure of the human IL-15-IL-15Ralpha complex. The structure provides insight into the molecular basis of the specificity of cytokine recognition and emphasizes the importance of water in generating this very high-affinity complex. Despite very low IL-15-IL-2 sequence homology and distinct receptor architecture, the topologies of the IL-15-IL-15Ralpha and IL-2-IL-2Ralpha complexes are very similar. Our data raise the possibility that IL-2, like IL-15, might be capable of being presented in trans in the context of its unique receptor alpha-chain.

Articles - 2z3r mentioned but not cited (3)

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  3. Identification of a gene for an ancient cytokine, interleukin 15-like, in mammals; interleukins 2 and 15 co-evolved with this third family member, all sharing binding motifs for IL-15Rα. Dijkstra JM, Takizawa F, Fischer U, Friedrich M, Soto-Lampe V, Lefèvre C, Lenk M, Karger A, Matsui T, Hashimoto K. Immunogenetics 66 93-103 (2014)


Reviews citing this publication (10)

  1. Structural biology of shared cytokine receptors. Wang X, Lupardus P, Laporte SL, Garcia KC. Annu Rev Immunol 27 29-60 (2009)
  2. Insights into cytokine-receptor interactions from cytokine engineering. Spangler JB, Moraga I, Mendoza JL, Garcia KC. Annu Rev Immunol 33 139-167 (2015)
  3. The shared and contrasting roles of IL2 and IL15 in the life and death of normal and neoplastic lymphocytes: implications for cancer therapy. Waldmann TA. Cancer Immunol Res 3 219-227 (2015)
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  9. Engineering cytokines for cancer immunotherapy: a systematic review. Fu Y, Tang R, Zhao X. Front Immunol 14 1218082 (2023)
  10. A method for making alignments of related protein sequences that share very little similarity; shark interleukin 2 as an example. Dijkstra JM. Immunogenetics 73 35-51 (2021)

Articles citing this publication (41)



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