APETx1 from Sea Anemone Anthopleura elegantissima Is a Gating Modifier Peptide Toxin of the Human Ether-a-go-go- Related Potassium Channel

2007 ◽  
Vol 72 (2) ◽  
pp. 259-268 ◽  
Author(s):  
M. Zhang ◽  
X.-S. Liu ◽  
S. Diochot ◽  
M. Lazdunski ◽  
G.-N. Tseng
Keyword(s):  
Potassium Channel ◽  
Sea Anemone ◽  
Anthopleura Elegantissima ◽  
Gating Modifier ◽  
Peptide Toxin

scholarly journals Mechanism of hERG inhibition by gating-modifier toxin, APETx1, deduced by functional characterization

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kazuki Matsumura ◽  
Takushi Shimomura ◽  
Yoshihiro Kubo ◽  
Takayuki Oka ◽  
Naohiro Kobayashi ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Resting State ◽  
Mutational Analysis ◽  
Functional Characterization ◽  
Structural Basis ◽  
Anthopleura Elegantissima ◽  
Gating Modifier ◽  
Peptide Toxin ◽  
Key Residues ◽  
Voltage Sensing Domain

Abstract Background Human ether-à-go-go-related gene potassium channel 1 (hERG) is a voltage-gated potassium channel, the voltage-sensing domain (VSD) of which is targeted by a gating-modifier toxin, APETx1. APETx1 is a 42-residue peptide toxin of sea anemone Anthopleura elegantissima and inhibits hERG by stabilizing the resting state. A previous study that conducted cysteine-scanning analysis of hERG identified two residues in the S3-S4 region of the VSD that play important roles in hERG inhibition by APETx1. However, mutational analysis of APETx1 could not be conducted as only natural resources have been available until now. Therefore, it remains unclear where and how APETx1 interacts with the VSD in the resting state. Results We established a method for preparing recombinant APETx1 and determined the NMR structure of the recombinant APETx1, which is structurally equivalent to the natural product. Electrophysiological analyses using wild type and mutants of APETx1 and hERG revealed that their hydrophobic residues, F15, Y32, F33, and L34, in APETx1, and F508 and I521 in hERG, in addition to a previously reported acidic hERG residue, E518, play key roles in the inhibition of hERG by APETx1. Our hypothetical docking models of the APETx1-VSD complex satisfied the results of mutational analysis. Conclusions The present study identified the key residues of APETx1 and hERG that are involved in hERG inhibition by APETx1. These results would help advance understanding of the inhibitory mechanism of APETx1, which could provide a structural basis for designing novel ligands targeting the VSDs of KV channels.

Isolation and cDNA cloning of a potassium channel peptide toxin from the sea anemone Anemonia erythraea

Toxicon ◽  
2006 ◽  
Vol 48 (5) ◽  
pp. 536-542 ◽  
Author(s):  
Yuichi Hasegawa ◽  
Tomohiro Honma ◽  
Hiroshi Nagai ◽  
Masami Ishida ◽  
Yuji Nagashima ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Cdna Cloning ◽  
Sea Anemone ◽  
Peptide Toxin

scholarly journals Identification of a novel type of processing sites in the precursor for the sea anemone neuropeptide Antho-RFamide (

1992 ◽  
Vol 267 (31) ◽  
pp. 22534-22541
Author(s):  
C Schmutzler ◽  
D Darmer ◽  
D Diekhoff ◽  
C.J. Grimmelikhuijzen
Keyword(s):  
Sea Anemone ◽  
Anthopleura Elegantissima

scholarly journals Corrigendum to “Structure, folding and stability of a minimal homologue from Anemonia sulcata of the sea anemone potassium channel blocker ShK” [Peptides 99 (2018) 169–178]

Peptides ◽  
2018 ◽  
Vol 101 ◽  
pp. 234
Author(s):  
Bankala Krishnarjuna ◽  
Christopher A. MacRaild ◽  
Punnepalli Sunanda ◽  
Rodrigo A.V. Morales ◽  
Steve Peigneur ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Channel Blocker ◽  
Sea Anemone ◽  
Potassium Channel Blocker ◽  
Anemonia Sulcata

Differential protein profiles reflect the different lifestyles of symbiotic and aposymbiotic Anthopleura elegantissima, a sea anemone from temperate waters

1996 ◽  
Vol 199 (4) ◽  
pp. 883-892
Author(s):  
V M Weis ◽  
R P Levine
Keyword(s):  
Steady State ◽  
Regulation Of Gene Expression ◽  
Sea Anemone ◽  
Protein Profiles ◽  
Post Translational Modification ◽  
Two Dimensional Gel Electrophoresis ◽  
Differential Protein ◽  
Algal Symbionts ◽  
Anthopleura Elegantissima ◽  
Endodermal Cells

Mutualistic associations are prevalent in virtually all environments yet relatively little is known about their complex biochemical and molecular integration and regulation. The endosymbiosis between cnidarians such as the sea anemone Anthopleura elegantissima and the photosynthetic dinoflagellate Symbiodinium californium, in which the algal symbionts are housed in vacuoles within animal endodermal cells, is an ideal model for the study of highly integrated associations at the biochemical and molecular levels. This study describes differential protein synthesis between symbiotic A. elegantissima, collected from environments with high levels of light in the intertidal zone and A. elegantissima that naturally lack symbionts (aposymbiotic), collected from nearby deep-shade habitats. Two-dimensional gel electrophoresis profiles of both steady-state and newly synthesized proteins were compared between the two types of animals using scanning densitometry and image analysis. Symbiotic and aposymbiotic animals share a majority of proteins; however, striking differences in several abundant proteins in steady-state profiles occur. Two proteins are unique to symbiotic animals, one at 32 kDa with an isoelectric point (pI) of 7.9 and another at 31 kDa, pI 6.3. Levels of six proteins with an apparent molecular mass of 25 kDa and pI values ranging from 4.8 to 5.5 are greatly enhanced in aposymbiotic animals. Furthermore, profiles of newly synthesized proteins from symbiotic animals contain a unique cluster of proteins ranging from 25 to 30 kDa and pI 6.6 to 6.9. These marked differences in protein profiles must be a reflection either of underlying differences in the regulation of gene expression or in post-translational modification of common proteins. Identifying the symbiosis-specific products present in A. elegantissima and identifying the inter-partner signaling and cues that result in differential expression will provide an insight into the understanding of these highly integrated associations.

Assignment of the three disulfide bonds in ShK toxin: A potent potassium channel inhibitor from the sea anemone Stichodactyla helianthus

1995 ◽  
Vol 1 (6) ◽  
pp. 291-297 ◽  
Author(s):  
Jan Pohl ◽  
Frantisek Hubalek ◽  
Michael E. Byrnes ◽  
Kurt R. Nielsen ◽  
Amina Woods ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Disulfide Bonds ◽  
Sea Anemone ◽  
Toxin A

scholarly journals Variation of Two S3b Residues in KV4.1–4.3 Channels Underlies Their Different Modulations by Spider Toxin κ-LhTx-1

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhen Xiao ◽  
Piao Zhao ◽  
Xiangyue Wu ◽  
Xiangjin Kong ◽  
Ruiwen Wang ◽  
...  
Keyword(s):  
Mutation Analysis ◽  
Voltage Dependence ◽  
Underlying Mechanism ◽  
Voltage Sensor ◽  
Action Mode ◽  
Gating Modifier ◽  
Peptide Toxin ◽  
Peptide Toxins ◽  
Key Residues ◽  
Animal Venoms

The naturally occurred peptide toxins from animal venoms are valuable pharmacological tools in exploring the structure-function relationships of ion channels. Herein we have identified the peptide toxin κ-LhTx-1 from the venom of spider Pandercetes sp (the Lichen huntsman spider) as a novel selective antagonist of the KV4 family potassium channels. κ-LhTx-1 is a gating-modifier toxin impeded KV4 channels’ voltage sensor activation, and mutation analysis has confirmed its binding site on channels’ S3b region. Interestingly, κ-LhTx-1 differently modulated the gating of KV4 channels, as revealed by toxin inhibiting KV4.2/4.3 with much more stronger voltage-dependence than that for KV4.1. We proposed that κ-LhTx-1 trapped the voltage sensor of KV4.1 in a much more stable resting state than that for KV4.2/4.3 and further explored the underlying mechanism. Swapping the non-conserved S3b segments between KV4.1(280FVPK283) and KV4.3(275VMTN278) fully reversed their voltage-dependence phenotypes in inhibition by κ-LhTx-1, and intensive mutation analysis has identified P282 in KV4.1, D281 in KV4.2 and N278 in KV4.3 being the key residues. Furthermore, the last two residues in this segment of each KV4 channel (P282/K283 in KV4.1, T280/D281 in KV4.2 and T277/N278 in KV4.3) likely worked synergistically as revealed by our combinatorial mutations analysis. The present study has clarified the molecular basis in KV4 channels for their different modulations by κ-LhTx-1, which have advanced our understanding on KV4 channels’ structure features. Moreover, κ-LhTx-1 might be useful in developing anti-arrhythmic drugs given its high affinity, high selectivity and unique action mode in interacting with the KV4.2/4.3 channels.

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