The Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket
| Autor: | Benjamin J. Doranz, Cheryl Paes, Bridget A. Puffer, Chidananda Sulli, Anu Thomas, Eli Berdougo, Joseph Rucker, Edgar Davidson, Morganne Phillips |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Science Plasma protein binding Biology medicine.disease_cause Article Receptors G-Protein-Coupled Substrate Specificity 03 medical and health sciences 0302 clinical medicine medicine Humans Glycosides Binding site Receptor G protein-coupled receptor Mutation Binding Sites Multidisciplinary Ligand HEK 293 cells Molecular Docking Simulation HEK293 Cells 030104 developmental biology Biochemistry Medicine Signal transduction 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-15 (2017) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Although bitter taste receptors (TAS2Rs) are important for human health, little is known of the determinants of ligand specificity. TAS2Rs such as TAS2R16 help define gustatory perception and dietary preferences that ultimately influence human health and disease. Each TAS2R must accommodate a broad diversity of chemical structures while simultaneously achieving high specificity so that diverse bitter toxins can be detected without all foods tasting bitter. However, how these G protein-coupled receptors achieve this balance is poorly understood. Here we used a comprehensive mutation library of human TAS2R16 to map its interactions with existing and novel agonists. We identified 13 TAS2R16 residues that contribute to ligand specificity and 38 residues whose mutation eliminated signal transduction by all ligands, providing a comprehensive assessment of how this GPCR binds and signals. Our data suggest a model in which hydrophobic residues on TM3 and TM7 form a broad ligand-binding pocket that can accommodate the diverse structural features of β-glycoside ligands while still achieving high specificity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|