Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site

Interleukin 10 (IL-10) is a dimeric cytokine that plays a central role in s uppressing inflammatory responses. These activities are dependent on the in teraction of IL-10 with its high-affinity receptor (IL-10R1). This intermed iate complex must subsequently recruit the low-affinity IL-10R2 chain befor e cell signaling can occur. Here we report the 2.9 Angstrom crystal structu re of IL-10 bound to a soluble form of IL-10R1 (sIL-10R1). The complex cons ists of two IL-10s and four sIL-10R1 molecules. Several residues in the IL- 10/sIL-10R1 interface are conserved in all IL-10 homologs and their recepto rs. The data suggests that formation of the active IL-10 signaling complex occurs by a novel molecular recognition paradigm where IL-10R1 and IL-10R2 both recognize the same binding site on IL-10.