9nvs | pdb_00009nvs
Structure of a pentameric Nanchung in complex with Afidopyropen
Structural highlights
Publication Abstract from PubMedInsecticides 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(2+)-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(2+). Visualizing insecticide control of insect TRP channel function and assembly.,Fedor JG, Kandasamy R, Park CG, Suo Y, Weisel M, Rankl NB, Nesterov A, Lee SY Nat Commun. 2025 Dec 14;17(1):595. doi: 10.1038/s41467-025-67287-2. PMID:41392056[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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