Conservation, amino-aromatic interactions

In addition to the DCTAE/DDTAV motifs, a highly conserved repetitive strand turn motif rich in aromatic amino acids (the QW motif) occurs in all OSCs and SCs and is repeated four to eight times (Table 3). These repeats are likely to be important for protein structure and stability and also for catalytic activity [55, 62-64]. The aromatic amino acids of the QW motif have been proposed to constitute sites of negative point charge that may interact with the intermediate cations during the cyclisation process [62]. 

A/B loop of the cytokine, forming a sheet-Uke structure with the A/B loop (Fig. 6, top). In both the viral and human IL-6 site II complexes, the A/B loop is ordered, whereas this loop I disordered in most unUganded cytokines. In both the viral IL-6 and human IL-6 site II interfaces, a Trp residue (Trp and Trp respectively) forms the heart of the interfaces, burying more surface than any other residues (Fig. 6, Fig. 7A). The placement of this aromatic residue is a conserved feature of aU gplSO-cytokines and so likely represents the site III hotspot. This central Trp is surrounded by a chemically diverse array of amino acids to make up a very large interaction surface with the gplSO D1 domain. In fact, many of the contacts are main chain Van der Waals and hydrogen bonds with the... 

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