Document Type
Article
Original Publication Date
2003
Journal/Book/Conference Title
The Biophysical Journal
Volume
84
Issue
5
First Page
3022
Last Page
3036
DOI of Original Publication
10.1016/S0006-3495(03)70028-9
Date of Submission
February 2015
Abstract
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.
Rights
From The Biophysical Journal, Zhang, M., Korolkova, Y.V., Liu, M., et al., BeKm-1 Is a HERG-Specific Toxin that Shares the Structure with ChTx but the Mechanism of Action with ErgTx1, Vol. 84, Page 3022. Copyright © 2003 The Biophysical Society. Published by Elsevier Inc. Reprinted with permission.
Is Part Of
VCU Physiology and Biophysics Publications
Comments
Originally published at http://dx.doi.org/10.1016/S0006-3495(03)70028-9
Under an Elsevier user license