Loading
PDBj
MenuPDBj@FacebookPDBj@TwitterPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

7W77

cryo-EM structure of human NaV1.3/beta1/beta2-bulleyaconitineA

Summary for 7W77
Entry DOI10.2210/pdb7w77/pdb
EMDB information32341
DescriptorSodium channel subunit beta-1, Sodium channel subunit beta-2, Sodium channel protein type 3 subunit alpha, ... (9 entities in total)
Functional Keywordsion channel, drug, antagonist, membrane protein
Biological sourceHomo sapiens (human)
More
Total number of polymer chains3
Total formula weight285991.70
Authors
Jiang, D.,Li, X. (deposition date: 2021-12-03, release date: 2022-04-06, Last modification date: 2024-10-30)
Primary citationLi, X.,Xu, F.,Xu, H.,Zhang, S.,Gao, Y.,Zhang, H.,Dong, Y.,Zheng, Y.,Yang, B.,Sun, J.,Zhang, X.C.,Zhao, Y.,Jiang, D.
Structural basis for modulation of human Na V 1.3 by clinical drug and selective antagonist.
Nat Commun, 13:1286-1286, 2022
Cited by
PubMed Abstract: Voltage-gated sodium (Na) channels play fundamental roles in initiating and propagating action potentials. Na1.3 is involved in numerous physiological processes including neuronal development, hormone secretion and pain perception. Here we report structures of human Na1.3/β1/β2 in complex with clinically-used drug bulleyaconitine A and selective antagonist ICA121431. Bulleyaconitine A is located around domain I-II fenestration, providing the detailed view of the site-2 neurotoxin binding site. It partially blocks ion path and expands the pore-lining helices, elucidating how the bulleyaconitine A reduces peak amplitude but improves channel open probability. In contrast, ICA121431 preferentially binds to activated domain IV voltage-sensor, consequently strengthens the Ile-Phe-Met motif binding to its receptor site, stabilizes the channel in inactivated state, revealing an allosterically inhibitory mechanism of Na channels. Our results provide structural details of distinct small-molecular modulators binding sites, elucidate molecular mechanisms of their action on Na channels and pave a way for subtype-selective therapeutic development.
PubMed: 35277491
DOI: 10.1038/s41467-022-28808-5
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.3 Å)
Structure validation

227111

PDB entries from 2024-11-06

PDB statisticsPDBj update infoContact PDBjnumon