Figure 2 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Conserved position E174 is part of the zinc binding triad and obeys the heptad pattern. Coiled-coils tend to follow the heptad pattern of HxxHCxC (H = hydrophobic, C = charged). (A) Helix 1 appears coiled with its antiparrallel partner helix 4. However the former does not follow the heptad pattern, and no coiled-coil signal was found by COILS, MultiCoil, or other expasy coiled-coil predictors. H18 and H21 are conserved (profile generated with Skylign, vertical size proportional to information) and part of the zinc binding triad. Thus the triad appears important for coiled-coiling (B) in the hGH monomer. Site 1 residues are shown in iceblue, remaining residues in cyan cartoons. At several positions, we generated mutations with binding kinetics similar to those of WT (green labels). We identified a second cluster of mutations with similar koff, but much slower kon (red labels). Mutants with kinetics that did not fall into either cluster are labelled in yellow. At some positions different substitutions were tested which produced different kinetics (M14E,W, S62Y,W, E174A,W,R). (C) Helix 4 follows the heptad pattern
Source publication
The interaction between human Growth Hormone (hGH) and hGH Receptor (hGHR) has great relevance to human diseases such as acromegaly and cancer. HGH has been extensively engineered by other workers to improve binding and other properties. We used a computational screen to select substitutions at single hGH positions within the hGHR-binding site. We...
