Document text
Principal Investigator: Joel Adam Butterwick
Organization: YALE UNIVERSITY
Fiscal Year: 2024
Award: $353,319
Funding agency: National Institute of General Medical Sciences
PROJECT SUMMARY
Animals desire sugars for their energy potential and for the pleasurable sensation of tasting sweetness. Despite
the importance of sugar receptors in influencing nutrient sensing, metabolic responses, and taste perception,
few studies have been performed to identify the molecular mechanisms underlying sugar detection and
recognition. The proposed project will address this gap by integrating structural and functional studies to offer a
unique perspective on the biophysical basis for sweet taste. In the first two Aims, we will focus on a single
exemplary GR, Gr9 from the silk moth Bombyx mori, and couple structural methods with mutagenesis and
functional assays to understand why it can only be activated by a single type of sugar, D-fructose. In Aim 1, we
will investigate how this receptor binds D-fructose, how binding is coupled to the channel gate, and how different
subunits within the tetramer interact cooperatively to open the ion-conducting pore. In Aim 2, we will investigate
why other similarly sized sugars bind but do not activate the channel. In Aim 3, we will expand our analysis to
other GRs that are activated by different sweet compounds to resolve the relationship between receptor
sequence and ligand specificity. Our structural and functional analyses of GRs will provide a crucial foundation
to understand how different tastants are recognized by a diverse collection of receptors and present novel routes
for the design and optimization of small molecules that interfere with the gustatory systems of insect vectors of
human pathogens.
Terms: <Affect><Afferent Neurons><Amino Acids><Animals><Assay><Binding><Bioassay><Biological Assay><Biophysics><Bombyx mori><Cations><Cell Body><Cells><Cessation of life><Chemicals><Chemoreceptors><Cognitive Discrimination><Collection><Complex><Coupled><Couples><Cues><Culicidae><D-Glucose><Data><Death><Detection><Dextrose><Disaccharides><Discrimination><Docking><Drosophila gustatory receptor><Esthesia><Family><Food><Foundations><Fructose><Genetics-Mutagenesis><Glucose><Gustation><Hexoses><Human><In Vitro><Insect Bites><Insect Vectors><Insecta><Insects><Insects Invertebrates><Ion Channel><Ionic Channels><Ions><Levulose><Life><Ligand Binding><Ligands><Link><Membrane Channels><Metabolic><Methods><Modeling><Modern Man><Molecular><Molecular Interaction><Mosquitoes><Moths><Mutagenesis><Mutagenesis Molecular Biology><Nutritional><Outcome><Pattern><Persons><Poison><Potential Energy><Receptor Protein><Role><Route><Saccharose><Sensation><Sensory Neurons><Side><Silk><Specificity><Structure><Sucrose><Taste><Taste Buds><Taste Perception><Toxic Chemical><Toxic Substance><Trehalose><aminoacid><analog><antagonism><antagonist><base><bases><biophysical foundation><biophysical principles><biophysical sciences><chemical group><design><designing><detection of nutrient><experiment><experimental research><experimental study><experiments><gustatory perception><gustatory processing><gustatory response><gustatory system><human pathogen><novel><nutrient sensing><nutritious><pathogen><perception of nutrients><receptor><receptor binding><receptor bound><response><small molecule><social role><structural biology><sugar><sweet taste><sweet taste perception><taste processing><taste receptor><taste response><taste system><tool><toxic compound>