title: Crystal structure of the IL-15-IL-15Ralpha complex, a cytokine-receptor unit presented in trans.
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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Chirifu
authors.forename: Chiharu
authors.initials: C
authors.lastname: Hayashi
authors.forename: Teruya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Sachiko
authors.initials: S
authors.lastname: Toma
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shuto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kai
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Yamagata
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Davis
authors.forename: Shinji
authors.initials: S
authors.lastname: Ikemizu
mesh_terms: D000595:Amino Acid Sequence; D003460:Crystallization; D006801:Humans; D019409:Interleukin-15 / Q000737:chemistry* / Q000235:genetics; D053720:Interleukin-15 Receptor alpha Subunit / Q000737:chemistry*; D007376:Interleukin-2 / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; D007376:Interleukin-2; D015375:Receptors, Interleukin-2