Canine interleukin-31 binds directly to OSMRβ with higher binding affinity than to IL-31RA

被引:0
|
作者
Zheng, Yuxin [1 ,2 ,3 ]
Zhang, Jing [2 ,3 ]
Guo, Tianling [2 ,3 ]
Cao, Jin [1 ,2 ,3 ]
Wang, Lixian [2 ,3 ]
Zhang, Jie [2 ,3 ]
Pang, Xuefei [2 ,3 ]
Gao, Feng [2 ,3 ]
Sun, Hua [1 ]
Xiao, Haixia [2 ,3 ]
机构
[1] Tianjin Univ Sci & Technol, Coll Biol Engn, Tianjin 300457, Peoples R China
[2] Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Lab Prot Engn & Vaccines, Tianjin 300308, Peoples R China
[3] Natl Technol Innovat Ctr Synthet Biol, Tianjin 300308, Peoples R China
关键词
Canine interleukin-31; IL-31 receptor alpha; Oncostatin M receptor beta; Binding affinity; STAT phosphorylation; ONCOSTATIN-M RECEPTOR; ATOPIC-DERMATITIS; CYTOKINE RECEPTOR; EPITHELIAL-CELLS; EXPRESSION; DISSECTION; FEATURES; TARGET; TRIAL; SKIN;
D O I
10.1007/s13205-023-03724-7
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Interleukin-31 (IL-31) is a pro-inflammatory cytokine involved in skin inflammation and tumor progression. The IL-31 signaling cascade is initiated by its binding to two receptors, IL-31 receptor alpha (IL-31RA) and oncostatin M receptor subunit beta (OSMR & beta;). The previous study suggested that human IL-31 (hIL-31) directly interacts with IL-31RA and OSMR & beta;, independently, but the binding ability of hIL-31 to IL-31RA is stronger than to OSMR & beta;. In different to its human ortholog, feline IL-31 (fIL-31) has a higher binding affinity for feline OSMR & beta;. However, the binding pattern of canine IL-31 to its receptors remains to be elucidated. In this study, we purified the recombinant canine IL-31 (rcIL-31) protein and revealed its secondary structure to be mainly composed of alpha-helices. Moreover, in vitro studies show that rcIL-31 has the ability to induce the phosphorylation of signal transducer activator of transcription 3 (STAT3) and STAT5 in DH-82 cells. In the following, the binding efficacies of bioactive rcIL-31 for its individual receptor components have been measured using a flow cytometry assay. The result demonstrates that correctly refolded rcIL-31 binds independently with cIL-31RA and cOSMR & beta; which were expressed on the cell surface. Of note, rcIL-31 has a greater than tenfold higher affinity to OSMR & beta; than to IL-31RA. Additionally, we demonstrated that D1-D4, especially D4 of cOSMR & beta;, is crucial for its binding to cIL-31. Furthermore, this study proved that rcIL-31 has a high binding affinity to the soluble cOSMR & beta; with a KD value of 3.59 x 10(-8) M. The results presented in the current study will have a significant implication in the development of drugs or antibodies against diseases induced by cIL-31 signaling.
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页数:11
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