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TitleStructural basis of ligand specificity and channel activation in an insect gustatory receptor.
Journal, issue, pagesCell Rep, Vol. 43, Issue 4, Page 114035, Year 2024
Publish dateApr 23, 2024
AuthorsHeather M Frank / Sanket Walujkar / Richard M Walsh / Willem J Laursen / Douglas L Theobald / Paul A Garrity / Rachelle Gaudet /
PubMed AbstractGustatory 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 ...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.
External linksCell Rep / PubMed:38573859 / PubMed Central
MethodsEM (single particle)
Resolution2.85 - 3.98 Å
Structure data

43129

8vc1

EMDB-43129, PDB-8vc1:
CryoEM structure of insect gustatory receptor BmGr9
Method: EM (single particle) / Resolution: 2.85 Å

43130

8vc2

EMDB-43130, PDB-8vc2:
CryoEM structure of insect gustatory receptor BmGr9 in the presence of fructose
Method: EM (single particle) / Resolution: 3.98 Å

Chemicals

ChemComp-PSC:
(7R,17E,20E)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-3,5,8-TRIOXA-4-PHOSPHAHEXACOSA-17,20-DIEN-1-AMINIUM 4-OXIDE / phospholipid*YM

ChemComp-PC7:
(7S)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-3,5,8-TRIOXA-4-PHOSPHAHEXACOSAN-1-AMINIUM 4-OXIDE / phospholipid*YM

ChemComp-9Z9:
(3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en / detergent*YM

Source
  • bombyx mori (domestic silkworm)
KeywordsMEMBRANE PROTEIN / gustatory receptor / homotetramer / ligand-gated ion channel / seven transmembrane

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