title: Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K(+) channel.
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. DOI:http://dx.doi.org/10.7554/eLife.00594.001.
authors.affiliation: Laboratory of Molecular Neurobiology and Biophysics , Rockefeller University , New York , United States ; Howard Hughes Medical Institute, Rockefeller University , New York , United States.
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
authors.forename: Alice
authors.initials: A
authors.lastname: Lee
authors.forename: Ernest
authors.initials: E
authors.lastname: Campbell
authors.forename: Roderick
authors.initials: R
authors.lastname: Mackinnon
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014118:Toxins, Biological / Q000737:chemistry* / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D014118:Toxins, Biological
keywords: Ion Channel; None; Scorpion toxin; Toxin; Voltage-dependent K+ Channel