Solution structure of μ-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels
Article
Article Title | Solution structure of μ-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels |
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ERA Journal ID | 2230 |
Article Category | Article |
Authors | Nielsen, Katherine J. (Author), Watson, Michael (Author), Adams, David J. (Author), Hammarstrom, Anna K. (Author), Gage, Peter W. (Author), Hill, Justine M. (Author), Craik, David J. (Author), Thomas, Linda (Author), Adams, Denise (Author), Alewood, Paul F. (Author) and Lewis, Richard J. (Author) |
Journal Title | Journal of Biological Chemistry |
Journal Citation | 277 (30), pp. 27247-27255 |
Number of Pages | 9 |
Year | 2002 |
Place of Publication | Bethesda, MD. United States |
ISSN | 0021-9258 |
1083-351X | |
Digital Object Identifier (DOI) | https://doi.org/10.1074/jbc.M201611200 |
Web Address (URL) | http://www.jbc.org/cgi/reprint/277/30/27247 |
Abstract | μ-Conotoxins are peptide inhibitors of voltage-sensitive sodium channels (VSSCs). Synthetic forms of μ-conotoxins PIIIA and PIIIA-(2-22) were found to inhibit tetrodotoxin (TTX)-sensitive VSSC current but had little effect on TTX-resistant VSSC current in sensory ganglion neurons. In rat brain neurons, these peptides preferentially inhibited the persistent over the transient VSSC current. Radioligand binding assays revealed that PIIIA, PIIIA-(2-22), and μ-conotoxin GIIIB discriminated among TTX-sensitive VSSCs in rat brain, that these and GIIIC discriminated among the corresponding VSSCs in human brain, and GIIIA had low affinity for neuronal VSSCs. 1H NMR studies found that PIIIA adopts two conformations in solution due to cis/trans isomerization at hydroxyproline 8. The major trans conformation results in a three-dimensional structure that is significantly different from the previously identified conformation of μ-conotoxins GIIIA and GIIIB that selectively target TTX-sensitive muscle VSSCs. Comparison of the structures and activity of PIIIA to muscle-selective μ-conotoxins provides an insight into the structural requirements for inhibition of different TTX-sensitive sodium channels by μ-conotoxins. |
Keywords | assays; brain; conformations; electric potential; muscle; isomerization; neurology; nuclear magnetic resonance; sodium |
ANZSRC Field of Research 2020 | 310104. Cell neurochemistry |
310111. Signal transduction | |
321407. Toxicology (incl. clinical toxicology) | |
Public Notes | © 2002 by The American Society for Biochemistry and Molecular Biology, Inc. Publisher does not formally support archiving. Published version made not accessible. |
Byline Affiliations | University of Queensland |
Department of Biological and Physical Sciences | |
Australian National University |
https://research.usq.edu.au/item/9y656/solution-structure-of-conotoxin-piiia-a-preferential-inhibitor-of-persistent-tetrodotoxin-sensitive-sodium-channels
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