28NO

CTX/MthK complex

Summary for 28NO

• Entry DOI: 10.2210/pdb28no/pdb
• EMDB information: 56657
• Descriptor: Potassium channel toxin alpha-KTx 1.1, Calcium-gated potassium channel MthK, POTASSIUM ION (3 entities in total)
• Functional Keywords: toxin-ion channel complex, membrane protein
• Biological source: Leiurus hebraeus; More
• Total number of polymer chains: 5
• Total formula weight: 157922.20

Authors

Qoraj, D.,Sprink, T.,Lange, A. (deposition date: 2026-02-10, release date: 2026-08-26, Last modification date: 2026-09-02)

Primary citation

Qoraj, D.,Mohr, S.,Aldakul, Y.K.,Sprink, T.,Oster, C.,Xiao, T.,Schmieder, P.,Lange, S.,Utesch, T.,Roderer, D.,Chen, S.,Sun, H.,Lange, A.
Atomic structure and plasticity of the CTX-MthK complex investigated by cryo-EM, NMR, and MD simulations.
Nat Commun, 17:-, 2026

PubMed Abstract: Scorpion toxins block potassium channels, disrupting cellular excitability and causing symptoms such as pain, muscle spasms, or paralysis. Here, we use an integrated structural biology approach to uncover the binding mode of the scorpion toxin charybdotoxin (CTX) to the MthK channel, a model system for human large-conductance potassium (BK) channels. Cryo-EM defines the overall architecture of the MthK-CTX complex, while complementary solution- and solid-state NMR experiments identify key binding residues and show that toxin engagement alters the selectivity filter (SF) ion configuration without rearranging the filter itself. NMR and MD simulations further reveal an anchoring lysine residue stably inserted into the SF, while other contacts undergo fast NMR timescale dynamics. Together, these findings explain how CTX-like toxins maintain exceptionally high affinity while tolerating binding across multiple K⁺ channel subtypes, paving the way for site-specific extracellular modulation.

PubMed: 42624849
DOI: 10.1038/s41467-026-76925-2

Experimental method

ELECTRON MICROSCOPY (4.1 Å)