Journal: Cell / Year: 2017 Title: Cryo-EM Structure of the Open Human Ether-à-go-go-Related K Channel hERG. Authors: Weiwei Wang / Roderick MacKinnon Abstract: The human ether-à-go-go-related potassium channel (hERG, Kv11.1) is a voltage-dependent channel known for its role in repolarizing the cardiac action potential. hERG alteration by mutation or ...The human ether-à-go-go-related potassium channel (hERG, Kv11.1) is a voltage-dependent channel known for its role in repolarizing the cardiac action potential. hERG alteration by mutation or pharmacological inhibition produces Long QT syndrome and the lethal cardiac arrhythmia torsade de pointes. We have determined the molecular structure of hERG to 3.8 Å using cryo-electron microscopy. In this structure, the voltage sensors adopt a depolarized conformation, and the pore is open. The central cavity has an atypically small central volume surrounded by four deep hydrophobic pockets, which may explain hERG's unusual sensitivity to many drugs. A subtle structural feature of the hERG selectivity filter might correlate with its fast inactivation rate, which is key to hERG's role in cardiac action potential repolarization. Copyright: 2017 Elsevier Inc. All rights reserved.
A: 144.80128 Å / B: 144.80128 Å / C: 118.8992 Å α=β=γ: 90 deg.
CCP4 map header:
mode
Image stored as Reals
Å/pix. X/Y/Z
0.56562890625
0.56562890625
0.46444921875
M x/y/z
256
256
256
origin x/y/z
0.000
0.000
0.000
length x/y/z
144.801
144.801
118.899
α/β/γ
90.000
90.000
90.000
start NX/NY/NZ
0
0
0
NX/NY/NZ
256
256
256
MAP C/R/S
3
1
2
start NC/NR/NS
0
0
0
NC/NR/NS
256
256
256
D min/max/mean
-2.046
6.321
0.459
-
Supplemental data
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Sample components
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Entire human ether-a-go-go related K+ channel hERG
Entire
Name: human ether-a-go-go related K+ channel hERG Details: Truncated hERG construct hERGTs (amino acid residues 141-380 and 871-1005 deleted) with S631A mutation Number of components: 2
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Component #1: cellular-component, human ether-a-go-go related K+ channel hERG
Cellular-component
Name: human ether-a-go-go related K+ channel hERG Details: Truncated hERG construct hERGTs (amino acid residues 141-380 and 871-1005 deleted) with S631A mutation Recombinant expression: No
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