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

Journal article

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.

Authors: Chirifu, M; Hayashi, C; Nakamura, T; Toma, S; Shuto, T

• Publication status: Published
• Journal: Nature immunology
• Volume: 8
• Issue: 9
• Pages: 1001-1007
• Publication date: 2007-09-01
• DOI: 10.1038/ni1492
• EISSN: 1529-2916
• ISSN: 1529-2908
• Language: English
• Keywords: Structural Homology, Protein; Amino Acid Sequence; Crystallization; Humans; Molecular Sequence Data; Interleukin-15; Interleukin-2; Interleukin-15 Receptor alpha Subunit; Protein Binding; Sequence Homology, Amino Acid; Protein Structure, Quaternary; Receptors, Interleukin-2