scholarly journals Molecular basis of the interaction between gating modifier spider toxins and the voltage sensor of voltage-gated ion channels

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Carus H. Y. Lau ◽  
Glenn F. King ◽  
Mehdi Mobli
Keyword(s):  
Ion Channels ◽  
Molecular Basis ◽  
Voltage Sensor ◽  
Voltage Gated ◽  
Spider Toxins ◽  
Gating Modifier ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

scholarly journals Cryo-EM structure of the KvAP channel reveals a non-domain-swapped voltage sensor topology

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Xiao Tao ◽  
Roderick MacKinnon
Keyword(s):  
Ion Channels ◽  
Conformational Changes ◽  
Voltage Sensor ◽  
Structural Domains ◽  
Structural Class ◽  
Voltage Sensors ◽  
Voltage Gated ◽  
Voltage Dependent ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

Conductance in voltage-gated ion channels is regulated by membrane voltage through structural domains known as voltage sensors. A single structural class of voltage sensor domain exists, but two different modes of voltage sensor attachment to the pore occur in nature: domain-swapped and non-domain-swapped. Since the more thoroughly studied Kv1-7, Nav and Cav channels have domain-swapped voltage sensors, much less is known about non-domain-swapped voltage-gated ion channels. In this paper, using cryo-EM, we show that KvAP from Aeropyrum pernix has non-domain-swapped voltage sensors as well as other unusual features. The new structure, together with previous functional data, suggests that KvAP and the Shaker channel, to which KvAP is most often compared, probably undergo rather different voltage-dependent conformational changes when they open.

scholarly journals Molecular basis of permeation in voltage-gated ion channels.

1993 ◽  
Vol 72 (3) ◽  
pp. 491-496 ◽  
Author(s):  
G F Tomaselli ◽  
P H Backx ◽  
E Marban
Keyword(s):  
Ion Channels ◽  
Molecular Basis ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

scholarly journals A Hot Spot for the Interaction of Gating Modifier Toxins with Voltage-Dependent Ion Channels

2000 ◽  
Vol 116 (5) ◽  
pp. 637-644 ◽  
Author(s):  
Jeffrey R. Winterfield ◽  
Kenton J. Swartz
Keyword(s):  
Ion Channels ◽  
Hot Spot ◽  
Large Family ◽  
Na Channel ◽  
Binding Motif ◽  
Voltage Gated ◽  
Channel One ◽  
Gating Modifier ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

The gating modifier toxins are a large family of protein toxins that modify either activation or inactivation of voltage-gated ion channels. ω-Aga-IVA is a gating modifier toxin from spider venom that inhibits voltage-gated Ca2+ channels by shifting activation to more depolarized voltages. We identified two Glu residues near the COOH-terminal edge of S3 in the α1A Ca2+ channel (one in repeat I and the other in repeat IV) that align with Glu residues previously implicated in forming the binding sites for gating modifier toxins on K+ and Na+ channels. We found that mutation of the Glu residue in repeat I of the Ca2+ channel had no significant effect on inhibition by ω-Aga-IVA, whereas the equivalent mutation of the Glu in repeat IV disrupted inhibition by the toxin. These results suggest that the COOH-terminal end of S3 within repeat IV contributes to forming a receptor for ω-Aga-IVA. The strong predictive value of previous mapping studies for K+ and Na+ channel toxins argues for a conserved binding motif for gating modifier toxins within the voltage-sensing domains of voltage-gated ion channels.

scholarly journals Voltage-gated ion channels and gating modifier toxins

Toxicon ◽  
2007 ◽  
Vol 49 (2) ◽  
pp. 124-141 ◽  
Author(s):  
William A. Catterall ◽  
Sandrine Cestèle ◽  
Vladimir Yarov-Yarovoy ◽  
Frank H. Yu ◽  
Keiichi Konoki ◽  
...  
Keyword(s):  
Ion Channels ◽  
Voltage Gated ◽  
Gating Modifier ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

scholarly journals Helical Structure of the Cooh Terminus of S3 and Its Contribution to the Gating Modifier Toxin Receptor in Voltage-Gated Ion Channels

2001 ◽  
Vol 117 (3) ◽  
pp. 205-218 ◽  
Author(s):  
Yingying Li-Smerin ◽  
Kenton J. Swartz
Keyword(s):  
Ion Channels ◽  
Secondary Structure ◽  
Terminal Part ◽  
Alanine Scanning Mutagenesis ◽  
K Channels ◽  
Voltage Gated ◽  
Gating Modifier ◽  
Α Helix ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

The voltage-sensing domains in voltage-gated K+ channels each contain four transmembrane (TM) segments, termed S1 to S4. Previous scanning mutagenesis studies suggest that S1 and S2 are amphipathic membrane spanning α-helices that interface directly with the lipid membrane. In contrast, the secondary structure of and/or the environments surrounding S3 and S4 are more complex. For S3, although the NH2-terminal part displays significant helical character in both tryptophan- and alanine-scanning mutagenesis studies, the structure of the COOH-terminal portion of this TM is less clear. The COOH terminus of S3 is particularly interesting because this is where gating modifier toxins like Hanatoxin interact with different voltage-gated ion channels. To further examine the secondary structure of the COOH terminus of S3, we lysine-scanned this region in the drk1 K+ channel and examined the mutation-induced changes in channel gating and Hanatoxin binding affinity, looking for periodicity characteristic of an α-helix. Both the mutation-induced perturbation in the toxin–channel interaction and in gating support the presence of an α-helix of at least 10 residues in length in the COOH terminus of S3. Together with previous scanning mutagenesis studies, these results suggest that, in voltage-gated K+ channels, the entire S3 segment is helical, but that it can be divided into two parts. The NH2-terminal part of S3 interfaces with both lipid and protein, whereas the COOH-terminal part interfaces with water (where Hanatoxin binds) and possibly protein. A conserved proline residue is located near the boundary between the two parts of S3, arguing for the presence of a kink in this region. Several lines of evidence suggest that these structural features of S3 probably exist in all voltage-gated ion channels.

Voltage-Gated Ion Channels, New Targets in Anti-Cancer Research

2007 ◽  
Vol 2 (3) ◽  
pp. 189-202 ◽  
Author(s):  
Le Jean-Yves ◽  
Ouadid-Ahidouch Halima ◽  
Soriani Olivier ◽  
Besson Pierre ◽  
Ahidouch Ahmed ◽  
...  
Keyword(s):  
Cancer Research ◽  
Ion Channels ◽  
Voltage Gated ◽  
New Targets ◽  
Anti Cancer ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels
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