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PDBsum entry 2z3q

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Cytokine/cytokine receptor PDB id
2z3q
Contents
Protein chains
114 a.a.
81 a.a.
117 a.a.
77 a.a.
Waters ×228

References listed in PDB file
Key reference
Title Crystal structure of the il-15-Il-15ralpha complex, A cytokine-Receptor unit presented in trans.
Authors M.Chirifu, C.Hayashi, T.Nakamura, S.Toma, T.Shuto, H.Kai, Y.Yamagata, S.J.Davis, S.Ikemizu.
Ref. Nat Immunol, 2007, 8, 1001-1007. [DOI no: 10.1038/ni1492]
PubMed id 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.
Figure 1.
(a) Two IL-15–IL-15R complexes in the asymmetric unit of the P2[1]2[1]2 crystal form. One IL-15 molecule (magenta) forms a complex with one IL-15R molecule (cyan), which then associates with another complex of IL-15 (blue) and IL-15R (red). These two complexes have a noncrystallographic twofold relationship. (b) Superposition of dimers of IL-15–IL15R complexes from the P2[1]2[1]2 (red) and P2[1]2[1]2[1] (blue) crystals.
Figure 4.
(a) The IL-15–IL-15R complex: magenta, IL-15; cyan, IL-15R . The interface is divided into three regions (outlined): top, middle and bottom.
The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Immunol (2007, 8, 1001-1007) copyright 2007.
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