Figure 3: Highly coupled OR residues coincide with experimentally characterized functional regions.

(a) Positions with above-average EC strength (top 25% of sites, blue spheres) on the top-ranked model of OR85b (140_12; Supplementary Data 13; membrane-integral side view). Strongly coupled residues cluster around three regions of the model: (i) N-terminus, (ii) EL2, (iii) IL3 and along the span of TMH7. Many of the strongly coupled TMH7 residues do not feature in the contact map (Fig. 1b), because they were excluded as structural contacts with our standard transmembrane clash filter. (b) Experimentally characterized residues in different OR and ORCO proteins (spheres coloured by different shades of blue according to functional categorization; Supplementary Table 2) mapped onto the 3D model of OR85b (140_12), based on a sequence alignment of OR and ORCO sequences (Supplementary Data 2). Among many residues whose mutation have general deleterious effects on ion channel function, only a few residues influence ion selectivity (which are strong candidates for pore-lining residues), including two sites in ORCO (double asterisks marking residues at the extracellular end of TMH6 and TMH7) and two in a tuning OR (B. mori OR1) (single asterisks marking residues at the intracellular end of TMH5 and TMH6) (see text and Supplementary Table 2 for details).