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 suppressing inflammatory responses. These activities are dependent on the interaction of IL-10 with its high-affinity receptor (IL-10R1). This intermediate complex must subsequently recruit the low-affinity IL-10R2 chain before cell signaling can occur. Here we report the 2.9 A crystal structure of IL-10 bound to a soluble form of IL-10R1 (sIL-10R1). The complex consists 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 receptors. 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.
Josephson
K
K
Center for Macromolecular Crystallography, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Logsdon
N J
NJ
Walter
M R
MR
D000595:Amino Acid Sequence; D001665:Binding Sites; D003460:Crystallization; D016753:Interleukin-10 / Q000737:chemistry*; D008969:Molecular Sequence Data; D017471:Receptors, Interferon / Q000737:chemistry; D018123:Receptors, Interleukin / Q000737:chemistry*; D053701:Receptors, Interleukin-10; D000096743:Interferon gamma Receptor
D016753:Interleukin-10; D017471:Receptors, Interferon; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D000096743:Interferon gamma Receptor