[Folding@home] Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15

BOINC_News · Post by **BOINC_News** » Thu Dec 09, 2021 5:04 pm

Nat Immunol. 2012 Dec;13(12):1187-95. doi: 10.1038/ni.2449. Epub 2012 Oct 28. 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...

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