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| Title | Visualizing insecticide control of insect TRP channel function and assembly. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 17, Issue 1, Page 595, Year 2025 |
| Publish date | Dec 14, 2025 |
Authors | Justin G Fedor / Ramani Kandasamy / Cheon-Gyu Park / Yang Suo / Martin Weisel / Nancy B Rankl / Alexandre Nesterov / Seok-Yong Lee / ![]() |
| PubMed Abstract | Insecticides 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 links | Nat Commun / PubMed:41392056 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.49 - 3.28 Å |
| Structure data | EMDB-49844, PDB-9nvn: EMDB-49845, PDB-9nvo: EMDB-49846, PDB-9nvp: EMDB-49847, PDB-9nvq: EMDB-49848, PDB-9nvr: EMDB-49849, PDB-9nvs: |
| Chemicals | ![]() ChemComp-6OU: ![]() ChemComp-LBN: ![]() ChemComp-CA: ![]() ChemComp-D39: ![]() ChemComp-NCA: ![]() PDB-1b32: |
| Source |
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Keywords | TRANSPORT PROTEIN / Membrane protein / membrane channel |
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homo sapiens (human)
halyomorpha halys (brown marmorated stink bug)
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