4GS7

Structure of the Interleukin-15 quaternary complex

Summary for 4GS7

• Entry DOI: 10.2210/pdb4gs7/pdb
• Related: 2b5i 2z3q
• Descriptor: Interleukin-15, Interleukin-2 receptor subunit beta, Cytokine receptor common subunit gamma, ... (9 entities in total)
• Functional Keywords: cytokine, cytokine receptor, immunoregulatory, anti-tumor, anti-viral, reductive methylation, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 71795.02

Authors

Ring, A.M.,Ozkan, E.,Feng, D.,Garcia, K.C. (deposition date: 2012-08-27, release date: 2012-11-07, Last modification date: 2025-03-26)

Primary citation

Ring, A.M.,Lin, J.X.,Feng, D.,Mitra, S.,Rickert, M.,Bowman, G.R.,Pande, V.S.,Li, P.,Moraga, I.,Spolski, R.,Ozkan, E.,Leonard, W.J.,Garcia, K.C.
Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15.
Nat.Immunol., 13:1187-1195, 2012

PubMed Abstract: Interleukin 15 (IL-15) and IL-2 have distinct immunological functions even though both signal through the receptor subunit IL-2Rβ and the common γ-chain (γ(c)). Here we found that in the structure of the IL-15-IL-15Rα-IL-2Rβ-γ(c) quaternary complex, IL-15 binds to IL-2Rβ and γ(c) in a heterodimer nearly indistinguishable from that of the IL-2-IL-2Rα-IL-2Rβ-γ(c) complex, despite their different receptor-binding chemistries. IL-15Rα substantially increased the affinity of IL-15 for IL-2Rβ, and this allostery was required for IL-15 trans signaling. Consistent with their identical IL-2Rβ-γ(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-2Rα versus IL-15Rα determined cellular responsiveness. Our results provide new insights for the development of specific immunotherapeutics based on IL-15 or IL-2.

PubMed: 23104097
DOI: 10.1038/ni.2449

Experimental method

X-RAY DIFFRACTION (2.35 Å)