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Structure paper

TitleStructures of the honeybee GABA RDL receptor illuminate allosteric modulation.
Journal, issue, pagesNeuron, Year 2026
Publish dateFeb 6, 2026
AuthorsTatiana Labouré / Mayank Prakash Pandey / Eleftherios Zarkadas / Céline Juillan-Binard / Delphine Baud / Jacques Neyton / Thierry Cens / Matthieu Rousset / François Dehez / Pierre Charnet / Hugues Nury /
PubMed AbstractA large share of insecticides targets insect ion channels. In particular, the GABA RDL (resistant to dieldrin) receptor is targeted by old pore blockers or more recent allosteric modulators binding ...A large share of insecticides targets insect ion channels. In particular, the GABA RDL (resistant to dieldrin) receptor is targeted by old pore blockers or more recent allosteric modulators binding to a cavity of its transmembrane domain. Here, we describe three ligand-binding sites and the associated receptor conformations, using a combination of cryoelectron microscopy (cryo-EM), electrophysiology, and molecular dynamics. The GABA site geometry is well conserved with that of mammalian receptors, in line with the absence of orthosteric insecticide. The transmembrane modulation site, occupied here by abamectin, exists in a closed-pore conformation. We identify a second allosteric transmembrane site using a compound named chrodrimanin B. Structures also reveal the existence of a conformation-dependent PIP lipid site. We anticipate our results to be the starting point for investigations on the physiological modulation of insect GABA receptors. The honeybee receptor structures may also foster the search for species-specific, environmentally benign insecticides.
External linksNeuron / PubMed:41653930
MethodsEM (single particle)
Resolution2.56 - 3.2 Å
Structure data

54897

9she

EMDB-54897, PDB-9she:
Structure of the honeybee GABAA RDL receptor with GABA and Abamectin
Method: EM (single particle) / Resolution: 3.2 Å

54906

9sho

EMDB-54906, PDB-9sho:
Structure of the honeybee GABAA RDL receptor with GABA
Method: EM (single particle) / Resolution: 2.56 Å

54929

9sio

EMDB-54929, PDB-9sio:
Structure of the honeybee GABAA RDL receptor apo state
Method: EM (single particle) / Resolution: 2.9 Å

54930

9siq

EMDB-54930, PDB-9siq:
Structure of the honeybee GABAA RDL receptor with Chrodrimanin B
Method: EM (single particle) / Resolution: 2.96 Å

Chemicals

ChemComp-ABU:
GAMMA-AMINO-BUTANOIC ACID / neurotransmitter, inhibitor*YM

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

PDB-1jnz:
Structure of adenylylsulfate reductase from the hyperthermophilic Archaeoglobus fulgidus at 1.6 resolution

ChemComp-PT5:
[(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho / phospholipid*YM

PDB-1jn7:
Solution Structure of a CCHH mutant of the ninth CCHC Zinc Finger of U-shaped

Source
  • apis mellifera (honey bee)
KeywordsMEMBRANE PROTEIN / GABAA receptor / insect / neurotransmission / insecticides

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