The primary difference due to the G159D mutation in cTnC is the formation of strong and phosphorylation-independent bond across the bottom of the interdomain interface, particularly between cTnC Arg83 and Asp159; consequently, the range of hinge angles is reduced by this immobilization. This affects the location of the apparent fulcrum of the 'hinge' so that the phosphorylation-dependent changes in the peptides crossing the interdomain interface can result in opposite changes consistent with the functional abnormalities caused by the mutation.