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TitleVisualizing insecticide control of insect TRP channel function and assembly.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Page 595, Year 2025
Publish dateDec 14, 2025
AuthorsJustin G Fedor / Ramani Kandasamy / Cheon-Gyu Park / Yang Suo / Martin Weisel / Nancy B Rankl / Alexandre Nesterov / Seok-Yong Lee /
PubMed AbstractInsecticides are vital to combating world food shortages and transmission of vector-borne human diseases. Increasing insecticide resistance necessitates discovery of novel compounds against ...Insecticides are vital to combating world food shortages and transmission of vector-borne human diseases. Increasing insecticide resistance necessitates discovery of novel compounds against underutilized targets. Nanchung (Nan) and Inactive (Iav), the transient receptor potential vanilloid-type (TRPV) channels in insects, likely form a heteromeric channel (Nan-Iav) and are localized in mechanosensory chordotonal organs which confer gravitaxis, hearing and proprioception. Several insecticides, such as afidopyropen (AP), target Nan-Iav through unknown mechanisms. Effective against piercing-sucking (hemipteran) insects, AP disrupts chordotonal functions preventing feeding. AP can bind to Nan alone, but only Nan-Iav exhibits channel activity with agonists including endogenous nicotinamide (NAM). Despite its importance as an insecticide target, much is unknown about Nan-Iav, such as channel assembly, modulator binding sites, and Ca-dependent regulation, hampering further insecticide development. Here we present the cryo-electron microscopy structures of hemipteran Nan-Iav with calmodulin bound in the apo state and with AP and NAM bound to cytosolic ankyrin repeat domain (ARD) interfaces. Unexpectedly, we found that Nan alone can form a pentamer, stabilized through AP-mediated ARD interactions. Our study provides molecular insights into insecticide and agonist interactions with Nan-Iav, highlighting the importance of the ARD on channel function and assembly, while also probing regulation by Ca.
External linksNat Commun / PubMed:41392056 / PubMed Central
MethodsEM (single particle)
Resolution2.49 - 3.28 Å
Structure data

EMDB-49844, PDB-9nvn:
Structure of Nanchung-Inactive-Calmodulin in apo state
Method: EM (single particle) / Resolution: 2.89 Å

EMDB-49845, PDB-9nvo:
Structure of Nanchung-Inactive-Calmodulin in complex with Nicotinamide
Method: EM (single particle) / Resolution: 2.49 Å

EMDB-49846, PDB-9nvp:
Structure of Nanchung-Inactive-Calmodulin in complex with Nicotinamide, EDTA
Method: EM (single particle) / Resolution: 2.85 Å

EMDB-49847, PDB-9nvq:
Structure of Nanchung-Inactive-Calmodulin in complex with Afidopyropen and calcium
Method: EM (single particle) / Resolution: 3.01 Å

EMDB-49848, PDB-9nvr:
Structure of Nanchung-Inactive-Calmodulin in complex with Afidopyropen, EDTA
Method: EM (single particle) / Resolution: 3.13 Å

EMDB-49849, PDB-9nvs:
Structure of a pentameric Nanchung in complex with Afidopyropen
Method: EM (single particle) / Resolution: 3.28 Å

Chemicals

ChemComp-6OU:
[(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate / phospholipid*YM

ChemComp-LBN:
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine / phospholipid*YM

ChemComp-CA:
Unknown entry

ChemComp-D39:
(2~{S})-2-azanyl-3-[[(2~{R})-3-hexadecanoyloxy-2-[(~{Z})-octadec-9-enoyl]oxy-propoxy]-oxidanyl-phosphoryl]oxy-propanoic acid

ChemComp-NCA:
NICOTINAMIDE / medication*YM

PDB-1b32:
OLIGO-PEPTIDE BINDING PROTEIN (OPPA) COMPLEXED WITH KMK

Source
  • homo sapiens (human)
  • halyomorpha halys (brown marmorated stink bug)
KeywordsTRANSPORT PROTEIN / Membrane protein / membrane channel

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