Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channel
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...
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eLife Sciences Publications Ltd
2013-05-01
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Online Access: | https://elifesciences.org/articles/00594 |
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author | Anirban Banerjee Alice Lee Ernest Campbell Roderick MacKinnon |
author_facet | Anirban Banerjee Alice Lee Ernest Campbell Roderick MacKinnon |
author_sort | Anirban Banerjee |
collection | DOAJ |
description | 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. |
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language | English |
last_indexed | 2024-04-12T12:15:46Z |
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spelling | doaj.art-6ed6a92ad5d44efbaa56a60015da36852022-12-22T03:33:26ZengeLife Sciences Publications LtdeLife2050-084X2013-05-01210.7554/eLife.00594Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channelAnirban Banerjee0Alice Lee1Ernest Campbell2Roderick MacKinnon3Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, New York, United States; Howard Hughes Medical Institute, Rockefeller University, New York, United StatesLaboratory of Molecular Neurobiology and Biophysics, Rockefeller University, New York, United States; Howard Hughes Medical Institute, Rockefeller University, New York, United StatesLaboratory of Molecular Neurobiology and Biophysics, Rockefeller University, New York, United States; Howard Hughes Medical Institute, Rockefeller University, New York, United StatesLaboratory of Molecular Neurobiology and Biophysics, Rockefeller University, New York, United States; Howard Hughes Medical Institute, Rockefeller University, New York, United StatesPore-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.https://elifesciences.org/articles/00594Ion ChannelToxinVoltage-dependent K+ ChannelScorpion toxin |
spellingShingle | Anirban Banerjee Alice Lee Ernest Campbell Roderick MacKinnon Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channel eLife Ion Channel Toxin Voltage-dependent K+ Channel Scorpion toxin |
title | Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channel |
title_full | Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channel |
title_fullStr | Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channel |
title_full_unstemmed | Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channel |
title_short | Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channel |
title_sort | structure of a pore blocking toxin in complex with a eukaryotic voltage dependent k channel |
topic | Ion Channel Toxin Voltage-dependent K+ Channel Scorpion toxin |
url | https://elifesciences.org/articles/00594 |
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