title: Taste substance binding elicits conformational change of taste receptor T1r heterodimer extracellular domains.
abstract: Sweet and umami tastes are perceived by T1r taste receptors in oral cavity. T1rs are class C G-protein coupled receptors (GPCRs), and the extracellular ligand binding domains (LBDs) of T1r1/T1r3 and T1r2/T1r3 heterodimers are responsible for binding of chemical substances eliciting umami or sweet taste. However, molecular analyses of T1r have been hampered due to the difficulties in recombinant expression and protein purification, and thus little is known about mechanisms for taste perception. Here we show the first molecular view of reception of a taste substance by a taste receptor, where the binding of the taste substance elicits a different conformational state of T1r2/T1r3 LBD heterodimer. Electron microscopy has showed a characteristic dimeric structure. Förster resonance energy transfer and X-ray solution scattering have revealed the transition of the dimerization manner of the ligand binding domains, from a widely spread to compactly organized state upon taste substance binding, which may correspond to distinct receptor functional states.
authors.affiliation: RIKEN SPring-8 Center, 1-1-1, Kouto, Sayo, Hyogo, 679-5148, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Nango
authors.affiliation: Research Center of Integrative Molecular System (CIMoS), Institute for Molecular Science, National Institute of Natural Sciences, 38 Nishigo-Naka, Myodaiji, Okazaki, Aichi, 444-8585, Japan.|Department of Functional Molecular Science, The Graduate University for Advanced Studies (SOKENDAI), 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Akiyama
authors.affiliation: RIKEN SPring-8 Center, 1-1-1, Kouto, Sayo, Hyogo, 679-5148, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Maki-Yonekura
authors.affiliation: RIKEN SPring-8 Center, 1-1-1, Kouto, Sayo, Hyogo, 679-5148, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ashikawa
authors.affiliation: Food Research Institute, NARO, 2-1-12, Kannondai, Tsukuba, Ibaraki, 305-8642, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kusakabe
authors.affiliation: Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Elena
authors.initials: E
authors.lastname: Krayukhina
authors.affiliation: Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Maruno
authors.affiliation: Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan.|Okazaki Institute for Integrative Biosciences, Okazaki, Aichi 444-8787, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Uchiyama
authors.affiliation: RIKEN SPring-8 Center, 1-1-1, Kouto, Sayo, Hyogo, 679-5148, Japan.|Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1, Tsushima-naka, Kita-ku, Okayama, 700-8530, Japan.
authors.forename: Nipawan
authors.initials: N
authors.lastname: Nuemket
authors.affiliation: RIKEN SPring-8 Center, 1-1-1, Kouto, Sayo, Hyogo, 679-5148, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yonekura
authors.affiliation: Food Research Institute, NARO, 2-1-12, Kannondai, Tsukuba, Ibaraki, 305-8642, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1, Tsushima-naka, Kita-ku, Okayama, 700-8530, Japan.
authors.forename: Nanako
authors.initials: N
authors.lastname: Atsumi
authors.affiliation: Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1, Tsushima-naka, Kita-ku, Okayama, 700-8530, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Yasui
authors.affiliation: RIKEN SPring-8 Center, 1-1-1, Kouto, Sayo, Hyogo, 679-5148, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hikima
authors.affiliation: RIKEN SPring-8 Center, 1-1-1, Kouto, Sayo, Hyogo, 679-5148, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: RIKEN SPring-8 Center, 1-1-1, Kouto, Sayo, Hyogo, 679-5148, Japan.|Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1, Tsushima-naka, Kita-ku, Okayama, 700-8530, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D005110:Extracellular Space / Q000737:chemistry*; D005973:Glutamine / Q000378:metabolism; D008024:Ligands; D009990:Oryzias; D000072417:Protein Domains; D055503:Protein Multimerization; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D011994:Recombinant Proteins / Q000378:metabolism; D053838:Scattering, Small Angle; D013649:Taste; D014961:X-Ray Diffraction
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; C431926:taste receptors, type 1; D005973:Glutamine