Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channel
Open Access
- 21 May 2013
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
- Vol. 2, e00594
- https://doi.org/10.7554/elife.00594
Abstract
Pore-blocking toxins inhibit voltage-dependent K+ channels (Kv channels) by plugging the ion-conduction pathway. We have solved the crystal structure of paddle chimera, a Kv channel in complex with charybdotoxin (CTX), a pore-blocking toxin. The toxin binds to the extracellular pore entryway without producing discernable alteration of the selectivity filter structure and is oriented to project its Lys27 into the pore. The most extracellular K+ binding site (S1) is devoid of K+ electron-density when wild-type CTX is bound, but K+ density is present to some extent in a Lys27Met mutant. In crystals with Cs+ replacing K+, S1 electron-density is present even in the presence of Lys27, a finding compatible with the differential effects of Cs+ vs K+ on CTX affinity for the channel. Together, these results show that CTX binds to a K+ channel in a lock and key manner and interacts directly with conducting ions inside the selectivity filter.Keywords
Funding Information
- Howard Hughes Medical Institute
- National Institutes of Health (GM 43949)
- Howard Hughes Medical Institute
- National Institutes of Health (GM 43949)
This publication has 63 references indexed in Scilit:
- Integrated Oxidative Folding of Cysteine/Selenocysteine Containing Peptides: Improving Chemical Synthesis of ConotoxinsAngewandte Chemie-International Edition, 2009
- Topology of the pore-region of a K+ channel revealed by the NMR-derived structures of scorpion toxinsNeuron, 1995
- An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantulaNeuron, 1995
- Solution structure of the potassium channel inhibitor agitoxin 2: Caliper for probing channel geometryProtein Science, 1995
- The charybdotoxin family of K+ channel-blocking peptidesNeuron, 1995
- Transfer of the scorpion toxin receptor to an insensitive potassium channelNeuron, 1994
- The charybdotoxin receptor of a Shaker K+ channel: Peptide and channel residues mediating molecular recognitionNeuron, 1994
- Atomic Structures of the Human Immunophilin FKBP-12 Complexes with FK506 and RapamycinJournal of Molecular Biology, 1993
- Interaction of charybdotoxin with permeant ions inside the pore of a K+ channelNeuron, 1992
- Mapping the receptor site for charybdotoxin, a pore-blocking potassium channel inhibitorNeuron, 1990