Structural basis of ligand specificity and channel activation in an insect gustatory receptor
Heather M. Frank,
Sanket Walujkar,
Richard M. Walsh, Jr.,
Willem J. Laursen,
Douglas L. Theobald,
Paul A. Garrity,
Rachelle Gaudet
Affiliations
Heather M. Frank
Department of Molecular and Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA
Sanket Walujkar
Department of Molecular and Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA
Richard M. Walsh, Jr.
The Harvard Cryo-EM Center for Structural Biology, Harvard Medical School, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
Willem J. Laursen
Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02453, USA
Douglas L. Theobald
Department of Biochemistry, Brandeis University, Waltham, MA 02453, USA
Paul A. Garrity
Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02453, USA; Corresponding author
Rachelle Gaudet
Department of Molecular and Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA; Corresponding author
Summary: Gustatory receptors (GRs) are critical for insect chemosensation and are potential targets for controlling pests and disease vectors, making their structural investigation a vital step toward 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 odorant receptors (ORs). Upon fructose binding, BmGr9’s channel gate opens through helix S7b movements. In contrast to ORs, BmGr9’s ligand-binding pocket, shaped by a kinked helix S4 and a shorter extracellular S3-S4 loop, is larger and solvent accessible in both agonist-free and fructose-bound states. Also, unlike ORs, fructose binding by BmGr9 involves helix S5 and a pocket lined with aromatic and polar residues. Structure-based sequence alignments reveal distinct patterns of ligand-binding pocket residue conservation in GR subfamilies associated with different ligand classes. These data provide insight into the molecular basis of GR ligand specificity and function.
