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.

journal_name

Elife

journal_title

eLife

authors

Banerjee A,Lee A,Campbell E,Mackinnon R

doi

10.7554/eLife.00594

subject

Has Abstract

pub_date

2013-05-21 00:00:00

pages

e00594

issn

2050-084X

pii

00594

journal_volume

2

pub_type

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