Crystal structure of a soluble decoy receptor IL-22BP bound to interleukin-22

Abstract 

Interleukin-22 (IL-22) plays an important role in the regulation of immune and inflammatory responses in mammals. The IL-22 binding protein (IL-22BP), a soluble receptor that specifically binds IL-22, prevents the IL-22/interleukin-22 receptor 1 (IL-22R1)/interleukin-10 receptor 2 (IL-10R2) complex assembly and blocks IL-22 biological activity. Here we present the crystal structure of the IL-22/IL-22BP complex at 2.75Å resolution. The structure reveals IL-22BP residues critical for IL-22 binding, which were confirmed by site-directed mutagenesis and functional studies. Comparison of IL-22/IL-22BP and IL-22/IL-22R1 crystal structures shows that both receptors display an overlapping IL-22 binding surface, which is consistent with the inhibitory role played by IL-22 binding protein.

Structured summary

MINT-7010533: IL-22 BP (uniprotkb:Q969J5) and IL-22 (uniprotkb:Q9GZX6) bind (MI:0407) by X-ray crystallography (MI:0114)

Abbreviations: IL-22BP, interleukin-22 binding protein, IL-22, interleukin-22, IL-22R1, interleukin-22 receptor 1, IL-10R2, interleukin-10 receptor 2, IL-10, interleukin 10, CRF2-9, cytokine receptor family class 2 member 9, CRF2-4, the second chain of the IL-10 receptor complex, CFR2-10, cytokine receptor family class 2 member 10, IL-22Rα2, IL-22 receptor subunit alpha-2, ORF, open reading frame, PDGF-R, platelet-derived growth factor receptor, FACS, fluorescent automatic cell sorter, FITC, fluorescein isothiocyanate, r.m.s.d., root mean square deviation, IL-10R1, interleukin-10 receptor 1, FBN-III, fibronectin-III domain

Keywords: Cytokine, IL-22, IL-22BP, Interleukin, Immunology, X-ray crystallography