Modulation of Ion Channels by Cysteine-Rich Peptides: From Sequence to Structure

Mobli, Mehdi, Undheim, Eivind A.B. and Rash, Lachlan D. (2017) Modulation of Ion Channels by Cysteine-Rich Peptides: From Sequence to Structure. Advances in Pharmacology, 79 199-223. doi:10.1016/bs.apha.2017.03.001

Author Mobli, Mehdi
Undheim, Eivind A.B.
Rash, Lachlan D.
Title Modulation of Ion Channels by Cysteine-Rich Peptides: From Sequence to Structure
Journal name Advances in Pharmacology   Check publisher's open access policy
ISSN 1557-8925
Publication date 2017-04-01
Year available 2017
Sub-type Article (original research)
DOI 10.1016/bs.apha.2017.03.001
Open Access Status Not yet assessed
Volume 79
Start page 199
End page 223
Total pages 25
Place of publication Maryland Heights, MO., United States
Publisher Academic Press
Language eng
Subject 3004 Pharmacology
Abstract Venom peptides are natural ligands of ion channels and have been used extensively in pharmacological characterization of various ion channels and receptors. In this chapter, we survey all known venom peptide ion-channel modulators. Our survey reveals that the majority of venom peptides characterized to date target voltage-gated sodium or potassium channels. We further find that the majority of these peptides are found in scorpion and spider venoms. We discuss the influence of the pharmacological tools available in biasing discovery and the classical "toxin-to-sequence" approach to venom peptide biodiscovery. The impact of high-throughput sequencing on the existing discovery framework is likely to be significant and we propose here an alternative "sequence-to-toxin" approach to peptide screening, relying more on recently developed high-throughput methods. Methods for production and characterization of disulfide rich toxins in a high-throughput setting are then described, focusing on bacterial protein expression and solution state structural characterization by NMR spectroscopy. Finally, the role of X-ray crystallography and cryo-EM are highlighted by discussing the currently known channel-peptide complexes.
Keyword Channel modulators
Cysteine-rich peptides
Disulfide-rich peptides
Gating modifier
Ion channels
Peptide structure
Pore blockers
Protein structure
Protein-protein interactions
Venom peptides
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
Centre for Advanced Imaging Publications
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Created: Sun, 31 Dec 2017, 20:17:39 EST