9NVO

Structure of Nanchung-Inactive-Calmodulin in complex with Nicotinamide

Summary for 9NVO

• Entry DOI: 10.2210/pdb9nvo/pdb
• EMDB information: 49845
• Descriptor: Inactive, Nanchung, Calmodulin-1, ... (8 entities in total)
• Functional Keywords: membrane protein, membrane channel, transport protein
• Biological source: Halyomorpha halys (brown marmorated stink bug); More
• Total number of polymer chains: 6
• Total formula weight: 454110.81

Authors

Fedor, J.G.,Lee, S.-Y. (deposition date: 2025-03-21, release date: 2026-02-11)

Primary citation

Fedor, J.G.,Kandasamy, R.,Park, C.G.,Suo, Y.,Weisel, M.,Rankl, N.B.,Nesterov, A.,Lee, S.Y.
Visualizing insecticide control of insect TRP channel function and assembly.
Nat Commun, 17:595-595, 2025

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 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.

PubMed: 41392056
DOI: 10.1038/s41467-025-67287-2

Experimental method

ELECTRON MICROSCOPY (2.49 Å)