4gs7
Structure of the Interleukin-15 quaternary complex
Structural highlights
FunctionIL15_HUMAN Cytokine that stimulates the proliferation of T-lymphocytes. Stimulation by IL-15 requires interaction of IL-15 with components of IL-2R, including IL-2R beta and probably IL-2R gamma but not IL-2R alpha. Publication Abstract from PubMedInterleukin 15 (IL-15) and IL-2 have distinct immunological functions even though both signal through the receptor subunit IL-2Rbeta and the common gamma-chain (gamma(c)). Here we found that in the structure of the IL-15-IL-15Ralpha-IL-2Rbeta-gamma(c) quaternary complex, IL-15 binds to IL-2Rbeta and gamma(c) in a heterodimer nearly indistinguishable from that of the IL-2-IL-2Ralpha-IL-2Rbeta-gamma(c) complex, despite their different receptor-binding chemistries. IL-15Ralpha substantially increased the affinity of IL-15 for IL-2Rbeta, and this allostery was required for IL-15 trans signaling. Consistent with their identical IL-2Rbeta-gamma(c) dimer geometries, IL-2 and IL-15 showed similar signaling properties in lymphocytes, with any differences resulting from disparate receptor affinities. Thus, IL-15 and IL-2 induced similar signals, and the cytokine specificity of IL-2Ralpha versus IL-15Ralpha determined cellular responsiveness. Our results provide new insights for the development of specific immunotherapeutics based on IL-15 or IL-2. Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15.,Ring AM, Lin JX, Feng D, Mitra S, Rickert M, Bowman GR, Pande VS, Li P, Moraga I, Spolski R, Ozkan E, Leonard WJ, Garcia KC Nat Immunol. 2012 Oct 28. doi: 10.1038/ni.2449. PMID:23104097[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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