FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2006393322> ?p ?o ?g. }

• W2006393322 endingPage "36041" @default.
• W2006393322 startingPage "36032" @default.
• W2006393322 abstract "The human bitter taste receptors (T2Rs) are non-Class A members of the G-protein-coupled receptor (GPCR) superfamily, with very limited structural information. Amino acid sequence analysis reveals that most of the important motifs present in the transmembrane helices (TM1–TM7) of the well studied Class A GPCRs are absent in T2Rs, raising fundamental questions regarding the mechanisms of activation and how T2Rs recognize bitter ligands with diverse chemical structures. In this study, the bitter receptor T2R1 was used to systematically investigate the role of 15 transmembrane amino acids in T2Rs, including 13 highly conserved residues, by amino acid replacements guided by molecular modeling. Functional analysis of the mutants by calcium imaging analysis revealed that replacement of Asn-662.65 and the highly conserved Asn-241.50 resulted in greater than 90% loss of agonist-induced signaling. Our results show that Asn-241.50 plays a crucial role in receptor activation by mediating an hydrogen bond network connecting TM1-TM2-TM7, whereas Asn-662.65 is essential for binding to the agonist dextromethorphan. The interhelical hydrogen bond between Asn-241.50 and Arg-552.54 restrains T2R receptor activity because loss of this bond in I27A and R55A mutants results in hyperactive receptor. The conserved amino acids Leu-1975.50, Ser-2005.53, and Leu-2015.54 form a putative LXXSL motif which performs predominantly a structural role by stabilizing the helical conformation of TM5 at the cytoplasmic end. This study provides for the first time mechanistic insights into the roles of the conserved transmembrane residues in T2Rs and allows comparison of the activation mechanisms of T2Rs with the Class A GPCRs. The human bitter taste receptors (T2Rs) are non-Class A members of the G-protein-coupled receptor (GPCR) superfamily, with very limited structural information. Amino acid sequence analysis reveals that most of the important motifs present in the transmembrane helices (TM1–TM7) of the well studied Class A GPCRs are absent in T2Rs, raising fundamental questions regarding the mechanisms of activation and how T2Rs recognize bitter ligands with diverse chemical structures. In this study, the bitter receptor T2R1 was used to systematically investigate the role of 15 transmembrane amino acids in T2Rs, including 13 highly conserved residues, by amino acid replacements guided by molecular modeling. Functional analysis of the mutants by calcium imaging analysis revealed that replacement of Asn-662.65 and the highly conserved Asn-241.50 resulted in greater than 90% loss of agonist-induced signaling. Our results show that Asn-241.50 plays a crucial role in receptor activation by mediating an hydrogen bond network connecting TM1-TM2-TM7, whereas Asn-662.65 is essential for binding to the agonist dextromethorphan. The interhelical hydrogen bond between Asn-241.50 and Arg-552.54 restrains T2R receptor activity because loss of this bond in I27A and R55A mutants results in hyperactive receptor. The conserved amino acids Leu-1975.50, Ser-2005.53, and Leu-2015.54 form a putative LXXSL motif which performs predominantly a structural role by stabilizing the helical conformation of TM5 at the cytoplasmic end. This study provides for the first time mechanistic insights into the roles of the conserved transmembrane residues in T2Rs and allows comparison of the activation mechanisms of T2Rs with the Class A GPCRs." @default.
• W2006393322 created "2016-06-24" @default.
• W2006393322 creator A5001516919 @default.
• W2006393322 creator A5010078532 @default.
• W2006393322 creator A5050967995 @default.
• W2006393322 creator A5089205384 @default.
• W2006393322 date "2011-10-01" @default.
• W2006393322 modified "2023-10-18" @default.
• W2006393322 title "Structural Basis of Activation of Bitter Taste Receptor T2R1 and Comparison with Class A G-protein-coupled Receptors (GPCRs)" @default.
• W2006393322 cites W1833104430 @default.
• W2006393322 cites W1972589601 @default.
• W2006393322 cites W1972615898 @default.
• W2006393322 cites W1973838813 @default.
• W2006393322 cites W1973858832 @default.
• W2006393322 cites W1975032814 @default.
• W2006393322 cites W1978990274 @default.
• W2006393322 cites W1979166300 @default.
• W2006393322 cites W1980374511 @default.
• W2006393322 cites W1986191025 @default.
• W2006393322 cites W1990205700 @default.
• W2006393322 cites W1995781028 @default.
• W2006393322 cites W2005193937 @default.
• W2006393322 cites W2010782393 @default.
• W2006393322 cites W2016264360 @default.
• W2006393322 cites W2028645925 @default.
• W2006393322 cites W2037312364 @default.
• W2006393322 cites W2052091241 @default.
• W2006393322 cites W2077046128 @default.
• W2006393322 cites W2077553389 @default.
• W2006393322 cites W2080231167 @default.
• W2006393322 cites W2097870001 @default.
• W2006393322 cites W2106648157 @default.
• W2006393322 cites W2109014958 @default.
• W2006393322 cites W2109159205 @default.
• W2006393322 cites W2113139507 @default.
• W2006393322 cites W2137015675 @default.
• W2006393322 cites W2137311570 @default.
• W2006393322 cites W2137714679 @default.
• W2006393322 cites W2159708799 @default.
• W2006393322 cites W2164431424 @default.
• W2006393322 cites W2166930152 @default.
• W2006393322 cites W4233523656 @default.
• W2006393322 doi "https://doi.org/10.1074/jbc.m111.246983" @default.
• W2006393322 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3195589" @default.
• W2006393322 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21852241" @default.
• W2006393322 hasPublicationYear "2011" @default.
• W2006393322 type Work @default.
• W2006393322 sameAs 2006393322 @default.
• W2006393322 citedByCount "67" @default.
• W2006393322 countsByYear W20063933222012 @default.
• W2006393322 countsByYear W20063933222013 @default.
• W2006393322 countsByYear W20063933222014 @default.
• W2006393322 countsByYear W20063933222015 @default.
• W2006393322 countsByYear W20063933222016 @default.
• W2006393322 countsByYear W20063933222017 @default.
• W2006393322 countsByYear W20063933222018 @default.
• W2006393322 countsByYear W20063933222019 @default.
• W2006393322 countsByYear W20063933222020 @default.
• W2006393322 countsByYear W20063933222021 @default.
• W2006393322 countsByYear W20063933222022 @default.
• W2006393322 crossrefType "journal-article" @default.
• W2006393322 hasAuthorship W2006393322A5001516919 @default.
• W2006393322 hasAuthorship W2006393322A5010078532 @default.
• W2006393322 hasAuthorship W2006393322A5050967995 @default.
• W2006393322 hasAuthorship W2006393322A5089205384 @default.
• W2006393322 hasBestOaLocation W20063933221 @default.
• W2006393322 hasConcept C104317684 @default.
• W2006393322 hasConcept C118892022 @default.
• W2006393322 hasConcept C135285700 @default.
• W2006393322 hasConcept C143065580 @default.
• W2006393322 hasConcept C167625842 @default.
• W2006393322 hasConcept C170493617 @default.
• W2006393322 hasConcept C185592680 @default.
• W2006393322 hasConcept C24530287 @default.
• W2006393322 hasConcept C2778938600 @default.
• W2006393322 hasConcept C47701112 @default.
• W2006393322 hasConcept C515207424 @default.
• W2006393322 hasConcept C55493867 @default.
• W2006393322 hasConcept C71240020 @default.
• W2006393322 hasConcept C86803240 @default.
• W2006393322 hasConceptScore W2006393322C104317684 @default.
• W2006393322 hasConceptScore W2006393322C118892022 @default.
• W2006393322 hasConceptScore W2006393322C135285700 @default.
• W2006393322 hasConceptScore W2006393322C143065580 @default.
• W2006393322 hasConceptScore W2006393322C167625842 @default.
• W2006393322 hasConceptScore W2006393322C170493617 @default.
• W2006393322 hasConceptScore W2006393322C185592680 @default.
• W2006393322 hasConceptScore W2006393322C24530287 @default.
• W2006393322 hasConceptScore W2006393322C2778938600 @default.
• W2006393322 hasConceptScore W2006393322C47701112 @default.
• W2006393322 hasConceptScore W2006393322C515207424 @default.
• W2006393322 hasConceptScore W2006393322C55493867 @default.
• W2006393322 hasConceptScore W2006393322C71240020 @default.
• W2006393322 hasConceptScore W2006393322C86803240 @default.
• W2006393322 hasIssue "41" @default.
• W2006393322 hasLocation W20063933221 @default.
• W2006393322 hasLocation W20063933222 @default.
• W2006393322 hasLocation W20063933223 @default.

• next