The cysteine-rich region of T1R3 determines responses to intensely sweet proteins.
A wide variety of chemically diverse compounds taste sweet, including natural sugars such as glucose, fructose, sucrose, and sugar alcohols, small molecule artificial sweeteners such as saccharin and acesulfame K, and proteins such as monellin and thaumatin. Brazzein, like monellin and thaumatin, is a naturally occurring plant protein that humans, apes, and Old World monkeys perceive as tasting sweet but that is not perceived as sweet by other species including New World monkeys, mouse, and rat. It has been shown that heterologous expression of T1R2 plus T1R3 together yields a receptor responsive to many of the above-mentioned sweet tasting ligands. We have determined that the molecular basis for species-specific sensitivity to brazzein sweetness depends on a site within the cysteine-rich region of human T1R3. Other mutations in this region of T1R3 affected receptor activity toward monellin, and in some cases, overall efficacy to multiple sweet compounds, implicating this region as a previously unrecognized important determinant of sweet receptor function.
Jiang
Peihua
P
Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029, USA.
Ji
Qingzhou
Q
Liu
Zhan
Z
Snyder
Lenore A
LA
Benard
Lumie M J
LM
Margolskee
Robert F
RF
Max
Marianna
M
D000409:Alanine / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D051379:Mice; D009154:Mutation; D010649:Phenylalanine / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry*; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013649:Taste; D013650:Taste Buds / Q000378:metabolism; D014162:Transfection
D010940:Plant Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; C090521:brazzein protein, Pentadiplandra brazzeana; C002541:monellin protein, Dioscoreophyllum cumminsii; C431926:taste receptors, type 1; D010649:Phenylalanine; D003545:Cysteine; D000409:Alanine