Locations of α0 domain HE/HPP mutations in the tetramer complex. Mutations that have been associated with HE or HPP are indicated as space-filling spheres on the ribbon diagram. Most of the mutations map directly to interacting residues. The relationship to our previously reported binding affinities with the use of isothermal titration calorimetry are color coded by the use of the previously defined binding affinity categories¹⁷ : red = severe (marginal or no detected binding); orange = moderate (∼100-fold weaker than wild type); yellow = modest (∼10-fold weaker than wild type); green = no effect (wild-type binding). (A) Mutations of positively charged residues. (B) Mutations of uncharged residues.