Figure 5

Simultaneous divergence at position 153 and 188 (from the correlation set 3) for HNF4 promotes a downstream displacement of the DBD:DNA interactions network. A and B are respectively RXR-DBD (PDB 2NLL) and PPAR-DBD (PDB 3DZY) at canonical half-sites. Red dashed circle show the hydrogen bond distance between E153 and the third antisense cytidine. C: model of HNF4 at the specific HRE (AGTCCA) with canonical replacements at the position 153 and 188. The red asterisk shows the loss of hydrogen interaction between E153 and the third anti-sense basis. D -The actual HNF4 (PDB 3CBB) presents E153D and Q188R co-substitutions simultaneously with K160R, allowing a global driving of the interaction network at the downstream sense and the favorable association with the AGTCCA HRE, HNF4 specific.