The mechanism of interaction of sweet proteins with the T1R2-T1R3 receptor: evidence from the solution structure of G16A-MNEI.
The mechanism by which sweet proteins elicit a response on the T1R2-T1R3 sweet taste receptor is still mostly unknown but has been so far related to the presence of "sweet fingers" on the protein surface able to interact with the same mechanism as that of low molecular mass sweeteners. In the search for the identification of sweet fingers, we have solved the solution structure of G16A MNEI, a structural mutant that shows a reduction of one order of magnitude in sweetness with respect to its parent protein, MNEI, a single-chain monellin. Comparison of the structures of wild-type monellin and its G16A mutant shows that the mutation does not affect the structure of potential glucophores but produces a distortion of the surface owing to the partial relative displacement of elements of secondary structure. These results show conclusively that sweet proteins do not possess a sweet finger and strongly support the hypothesis that the mechanism of interaction of sweet-tasting proteins with the recently identified T1R2-T1R3 GPC receptor is different from that of low molecular mass sweeteners.
Spadaccini
Roberta
R
Dipartimento di Chimica, Università di Napoli Federico II, Via Cinthia 45, 80126 Naples, Italy.
Trabucco
Franca
F
Saviano
Gabriella
G
Picone
Delia
D
Crescenzi
Orlando
O
Tancredi
Teodorico
T
Temussi
Piero A
PA
D001665:Binding Sites; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D017433:Protein Structure, Secondary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents / Q000737:chemistry; D013649:Taste
D010940:Plant Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; C002541:monellin protein, Dioscoreophyllum cumminsii; C431926:taste receptors, type 1; D019204:GTP-Binding Proteins