title: Characterization of the modes of binding between human sweet taste receptor and low-molecular-weight sweet compounds.
abstract: One of the most distinctive features of human sweet taste perception is its broad tuning to chemically diverse compounds ranging from low-molecular-weight sweeteners to sweet-tasting proteins. Many reports suggest that the human sweet taste receptor (hT1R2-hT1R3), a heteromeric complex composed of T1R2 and T1R3 subunits belonging to the class C G protein-coupled receptor family, has multiple binding sites for these sweeteners. However, it remains unclear how the same receptor recognizes such diverse structures. Here we aim to characterize the modes of binding between hT1R2-hT1R3 and low-molecular-weight sweet compounds by functional analysis of a series of site-directed mutants and by molecular modeling-based docking simulation at the binding pocket formed on the large extracellular amino-terminal domain (ATD) of hT1R2. We successfully determined the amino acid residues responsible for binding to sweeteners in the cleft of hT1R2 ATD. Our results suggest that individual ligands have sets of specific residues for binding in correspondence with the chemical structures and other residues responsible for interacting with multiple ligands.
authors.affiliation: Suntory Institute for Bioorganic Research, Mishima-gun, Osaka, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Masuda
authors.forename: Ayako
authors.initials: A
authors.lastname: Koizumi
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Nakajima
authors.forename: Takaharu
authors.initials: T
authors.lastname: Tanaka
authors.forename: Keiko
authors.initials: K
authors.lastname: Abe
authors.forename: Takumi
authors.initials: T
authors.lastname: Misaka
authors.forename: Masaji
authors.initials: M
authors.lastname: Ishiguro
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D001218:Aspartame / Q000737:chemistry; D001665:Binding Sites; D003198:Computer Simulation; D003494:Cyclamates / Q000737:chemistry / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D012439:Saccharin / Q000737:chemistry / Q000494:pharmacology; D013395:Sucrose / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D013549:Sweetening Agents / Q000737:chemistry* / Q000494:pharmacology; D013843:Thiazines / Q000737:chemistry / Q000494:pharmacology; D014364:Tryptophan / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003494:Cyclamates; D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; D013843:Thiazines; C431926:taste receptors, type 1; D013395:Sucrose; D014364:Tryptophan; C026285:trichlorosucrose; D012439:Saccharin; C006362:acetosulfame; D001218:Aspartame