7K18

Cardiac Sodium channel with toxin bound

Summary for 7K18

• Entry DOI: 10.2210/pdb7k18/pdb
• EMDB information: 22621
• Descriptor: Sodium channel protein type 5 subunit alpha, Enhanced Green fluorescent protein, Alpha-like toxin Lqh3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: ion channel, toxin bound, membrane protein
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 2
• Total formula weight: 225658.27

Authors

Jiang, D.,Catterall, W.A. (deposition date: 2020-09-07, release date: 2021-01-20, Last modification date: 2024-12-25)

Primary citation

Jiang, D.,Tonggu, L.,Gamal El-Din, T.M.,Banh, R.,Pomes, R.,Zheng, N.,Catterall, W.A.
Structural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin.
Nat Commun, 12:128-128, 2021

PubMed Abstract: Voltage-gated sodium (Na) channels initiate action potentials in excitable cells, and their function is altered by potent gating-modifier toxins. The α-toxin LqhIII from the deathstalker scorpion inhibits fast inactivation of cardiac Na1.5 channels with IC = 11.4 nM. Here we reveal the structure of LqhIII bound to Na1.5 at 3.3 Å resolution by cryo-EM. LqhIII anchors on top of voltage-sensing domain IV, wedged between the S1-S2 and S3-S4 linkers, which traps the gating charges of the S4 segment in a unique intermediate-activated state stabilized by four ion-pairs. This conformational change is propagated inward to weaken binding of the fast inactivation gate and favor opening the activation gate. However, these changes do not permit Na permeation, revealing why LqhIII slows inactivation of Na channels but does not open them. Our results provide important insights into the structural basis for gating-modifier toxin binding, voltage-sensor trapping, and fast inactivation of Na channels.

PubMed: 33397917
DOI: 10.1038/s41467-020-20078-3

Experimental method

ELECTRON MICROSCOPY (3.3 Å)