Crystal structure of the intensely sweet protein monellin

Two unusual proteins, discovered in African berries, possess the interesting property of having a very high specificity for the sweet receptors. These proteins, monellin^1,2 and thaumatin³, are approximately 100,000 times sweeter than sugar on a molar basis and several thousand times sweeter on a weight basis. Neither contains carbohydrates or modified amino acids. Several interesting observations have been made about the two proteins: native conformations are important for the sweet taste ^4-6, although both proteins are intensely sweet, there are no statistically significant sequence similarities between them⁷; and despite the absence of sequence similarity, antibodies against thaumatin compete for monellin (as well as many other sweet compounds^8,9, but not for chemically modified non-sweet monellin9) and vice versa¹⁰. To understand the structural basis of these observations we determined the crystal structure of thaumatin¹¹, and report here the structure of monellin at 3 Å resolution. Monellin consists of two peptide chains, the A chain of 44 residues and the B chain of 50 residues^12,13. We find no similarity between the backbone structure of monellin and that of thaumatin.