Figure 1. The IL-6R stalk region contains a 3S motif adjacent to the cleavage site.

(a) Sequence alignment of the juxtamembrane regions of TNFα , CD163 (according to¹⁴) and the IL-6R. The serine-rich motifs within the three proteins are indicated by gray background color, and the start of the transmembrane regions is indicated by the vertical black line. (b) The five non-prime and prime sites of the ADAM17 cleavage site within the IL-6R. The 3S motif is highlighted by the gray background. (c) Based on the known structure of the catalytic domain of ADAM17 in complex with TIMP3, a model of the catalytic domain (orange) in complex with the corresponding amino-acid residues of the IL-6R stalk region (colored in blue) was generated. Critical amino acids of ADAM17 are given. (d) Close-up of the catalytic center of ADAM17. The IL-6R peptide QDSSSVP is shown in green. (e) Hydrophobic patches on the surface of the catalytic domain of ADAM17 are colored in yellow. The IL-6R peptide is shown in red. (f) Close-up of the catalytic center of ADAM17. The IL-6R peptide PVQDSSS is shown in blue.