8T6L

Cryo-EM structure of rat cardiac sodium channel NaV1.5 with batrachotoxin analog BTX-B

Summary for 8T6L

• Entry DOI: 10.2210/pdb8t6l/pdb
• EMDB information: 41071
• Descriptor: Sodium channel protein type 5 subunit alpha,Green fluorescent protein, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• Functional Keywords: ion channel, sodium channel, voltage-gated channel, sodium transport, membrane protein
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 1
• Total formula weight: 231783.45

Authors

Tonggu, L.,Wisedchaisri, G.,Gamal El-Din, T.M.,Zheng, N.,Catterall, W.A. (deposition date: 2023-06-16, release date: 2024-03-06, Last modification date: 2024-03-27)

Primary citation

Tonggu, L.,Wisedchaisri, G.,Gamal El-Din, T.M.,Lenaeus, M.J.,Logan, M.M.,Toma, T.,Du Bois, J.,Zheng, N.,Catterall, W.A.
Dual receptor-sites reveal the structural basis for hyperactivation of sodium channels by poison-dart toxin batrachotoxin.
Nat Commun, 15:2306-2306, 2024

PubMed Abstract: The poison dart toxin batrachotoxin is exceptional for its high potency and toxicity, and for its multifaceted modification of the function of voltage-gated sodium channels. By using cryogenic electron microscopy, we identify two homologous, but nonidentical receptor sites that simultaneously bind two molecules of toxin, one at the interface between Domains I and IV, and the other at the interface between Domains III and IV of the cardiac sodium channel. Together, these two bound toxin molecules stabilize α/π helical conformation in the S6 segments that gate the pore, and one of the bound BTX-B molecules interacts with the crucial Lys1421 residue that is essential for sodium conductance and selectivity via an apparent water-bridged hydrogen bond. Overall, our structure provides insight into batrachotoxin's potency, efficacy, and multifaceted functional effects on voltage-gated sodium channels via a dual receptor site mechanism.

PubMed: 38485923
DOI: 10.1038/s41467-024-45958-w

Experimental method

ELECTRON MICROSCOPY (3.3 Å)