Five amino acid residues in cysteine-rich domain of human T1R3 were involved in the response for sweet-tasting protein, thaumatin

► Mutations in the CRD of hT1R3 were prepared to evaluate the response to thaumatin. ► Five residues in the CRD were found to be important for the response to thaumatin. ► These critical residues were widely dispersed compared to those in brazzein. ► The uniqueness of thaumatin may be attributed to a different receptor activation mechanism.