Structural basis of ligand specificity and channel activation in an insect gustatory receptor

Gustatory Receptors (GRs) are critical for insect chemosensation and are
potentialtargets for controlling pests and disease vectors, making their
structural investigation avital step towards such applications. We present
structures of Bombyx mori Gr9(BmGr9), a fructose-gated cation channel, in
agonist-free and fructose-bound states.BmGr9 forms a tetramer similar to
distantly related insect Olfactory Receptors (ORs).Upon fructose binding,
BmGr9’s channel gate opens through helix S7b movements. Incontrast to ORs,
BmGR9’s ligand-binding pocket, shaped by a kinked helix S4 and ashorter
extracellular S3-S4 loop, is larger and solvent accessible in both
agonist-freeand fructose-bound states. Also unlike ORs, fructose binding
by BmGr9 involves helixS5 and a pocket lined with aromatic and polar
residues. Structure-based sequencealignments reveal distinct patterns of
ligand-binding pocket residue conservation in GRsubfamilies associated
with different ligand classes. These data provide insight into
themolecular basis of GR ligand specificity and function.