The Interleukin-17 receptor A/C complex is a dimer of Interleukin-17 receptor A (IL17RA) and Interleukin-17 receptor C (IL17RC). It binds interleukin-17A (IL17A) dimers, IL17F dimers and IL17A:IL17F heterodimers (IL17A:IL17F) (Yao et al. 1995, Toy et al. 2006). IL17A and IL17F homodimers tend to disfavor binding of a second molecule of IL17RA to the receptor/ligand complex (Liu et al. 2013). Engagement of IL17RA or IL17RC by IL17A or IL17F brings about an allosteric 'preference' for the second receptor-binding site to engage a different receptor to form a heterodimeric receptor complex (Ely et al. 2003) This is a Black Box event because the order of receptor binding is unclear.
Secreted SARS-CoV-2 ORF8 (8) binds to IL17RA and activates IL17 signaling pathway leading to an increased secretion of cytokines/chemokines thus contributing to cytokine storm during SARS-CoV-2 infection (Lin X et al. 2021).
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