Referenced in: none

Automatically associated channels: Kv11.1

Title: BeKm-1 is a HERG-specific toxin that shares the structure with ChTx but the mechanism of action with ErgTx1.

Authors: Mei Zhang, Yuliya V Korolkova, Jie Liu, Min Jiang, Eugene V Grishin, Gea-Ny Tseng

Journal, date & volume: Biophys. J., 2003 May , 84, 3022-36

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12719233

Abstract
Peptide toxins with disulfide-stabilized structures have been used as molecular calipers to probe the outer vestibule structure of K channels. We want to apply this approach to the human ether-a-go-go-related gene (HERG) channel, whose outer vestibule is unique in structure and function among voltage-gated K channels. Our focus here is BeKm-1, a HERG-specific peptide toxin that can suppress HERG in the low nM concentration range. Although BeKm-1 shares the three-dimensional scaffold with the well-studied charybdotoxin, the two use different mechanisms in suppressing currents through their target K channels. BeKm-1 binds near, but not inside, the HERG pore, and it is possible that BeKm-1-bound HERG channels can conduct currents although with markedly altered voltage-dependence and kinetics of gating. BeKm-1 and ErgTx1 differ in three-dimensional scaffold, but the two share mechanism of action and have overlapping binding sites on the HERG channel. For both, residues in the middle of the S5-P linker (the putative 583-597 helix) and residues at the pore entrance are critical for binding, although specific contact points vary between the two. Toxin foot printing using BeKm-1 and ErgTx1 will likely provide complementary information about the unique outer vestibule structure of the HERG channel.