logo
ResearchBunny Logo
Structural basis for modulation of human Nav1.3 by clinical drug and selective antagonist

Medicine and Health

Structural basis for modulation of human Nav1.3 by clinical drug and selective antagonist

X. Li, F. Xu, et al.

Dive into the fascinating world of voltage-gated sodium channels! This study reveals how NaV1.3 interacts with specific modulators like bulleyaconitine A and ICA121431, shedding light on their unique binding mechanisms. Conducted by esteemed researchers including Xiaojing Li and Feng Xu, these findings are paving the way for targeted therapeutic advancements.

00:00
00:00
Playback language: English
Abstract
Voltage-gated sodium (NaV) channels are crucial for action potential initiation and propagation. NaV1.3 plays a significant role in various physiological processes, including neuronal development, hormone secretion, and pain perception. This study presents the structures of human NaV1.3/β1/β2 in complex with bulleyaconitine A (BLA) and the selective antagonist ICA121431. BLA binds near the domain I-II fenestration (site-2 neurotoxin binding site), partially blocking the ion path and expanding pore-lining helices, reducing peak amplitude but increasing open probability. Conversely, ICA121431 binds to the activated domain IV voltage sensor, strengthening the Ile-Phe-Met motif binding, stabilizing the channel in the inactivated state. These findings provide structural details of distinct modulator binding sites and elucidate their mechanisms of action on NaV channels, informing subtype-selective therapeutic development.
Publisher
Nature Communications
Published On
Mar 11, 2022
Authors
Xiaojing Li, Feng Xu, Hao Xu, Shuli Zhang, Yiwei Gao, Hongwei Zhang, Yanli Dong, Yanchun Zheng, Bei Yang, Jianyuan Sun, Xuejun Cai Zhang, Yan Zhao, Daohua Jiang
Tags
NaV channels
bulleyaconitine A
ICA121431
ion pathways
channel inactivation
modulator binding
therapeutic development

Related Publications

Explore these studies to deepen your understanding of the subject.

Structural basis for the activation of plant bunyavirus replication machinery and its dual-targeted inhibition by ribavirin
Biology

Structural basis for the activation of plant bunyavirus replication machinery and its dual-targeted inhibition by ribavirin

J. Li, L. Cao, et al.

A comparative study of COVID-19 transcriptional signatures between clinical samples and preclinical cell models in the search for disease master regulators and drug repositioning candidates
Medicine and Health

A comparative study of COVID-19 transcriptional signatures between clinical samples and preclinical cell models in the search for disease master regulators and drug repositioning candidates

H. Chapola, M. A. D. Bastiani, et al.

Discovery of a selective and biologically active low-molecular weight antagonist of human interleukin-1β
Medicine and Health

Discovery of a selective and biologically active low-molecular weight antagonist of human interleukin-1β

U. Hommel, K. Hurth, et al.

Connectome dysfunction in patients at clinical high risk for psychosis and modulation by oxytocin
Psychology

Connectome dysfunction in patients at clinical high risk for psychosis and modulation by oxytocin

C. Davies, D. Martins, et al.

Listen, Learn & Level Up
Over 10,000 hours of research content in 25+ fields, available in 12+ languages.
No more digging through PDFs, just hit play and absorb the world's latest research in your language, on your time.
listen to research audio papers with researchbunny