// NATURE NEWS — SPAZIO & SCIENZA
Structural basis of ligand recognition and gating in mosquito IRs
Nature
(2026) Cite this article
We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply.
Ionotropic receptors (IRs) are essential for insect olfaction, enabling the detection of carboxylic acids, amines, moisture, and temperature cues that mediate critical behaviors, including mosquito host-seeking 1,2. However, the structural mechanisms underlying ligand specificity and channel activation in these receptors remain unclear. Here, we report cryo-electron microscopy (cryo-EM) structures and functional validation of the IR8a-IR75k complex from the malaria mosquito Anopheles stephensi, a carboxylic acid detector, captured in four states: the ligand-free full-length closed form (apo state), the ligand induced full-length open state, and the nonanoic acid (NA)- and octanoic acid (OA)-bound extracellular domains. These structures reveal a dynamic ligand-binding pocket in IR75k, in which specificity is determined by alkyl chain length and carboxylate geometry. Ligand binding triggers closure of IR75k’s bilobed ligand binding domain (LBD), and this conformational change propagates through conserved mechanical linkers to the transmembrane domain (TMD), functioning as a molecular lever that dilates the pore via outward displacement of transmembrane helices. This gating mechanism was further corroborated by molecular dynamics simulations and electrophysiology. These insights provide an atomic resolution view of IR mediated host detection in mosquitoes and establish a foundation for the rational design of next generation mosquito control strategies targeting host-seeking behavior.
This is a preview of subscription content, access via your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
Prices may be subject to local taxes which are calculated during checkout
These authors contributed equally: Li Xu, Xin Wang, Xuebo Quan
Institute of Bio-Architecture and Bio-Interactions (IBABI), Shenzhen Medical Academy of Research and Translation (SMART), Shenzhen, Guangdong Province, China
Li Xu
(徐莉), Dong Liu
(刘东), Jiawei Chen
(陈嘉伟) & Xiaojing Pan
(潘孝敬)