1r9i
From Proteopedia
NMR Solution Structure of PIIIA toxin, NMR, 20 structures
Structural highlights
FunctionCM3A_CONPU Mu-conotoxins block voltage-gated sodium channels (Nav). This toxin potently blocks rNav1.4/SCN4A. It also moderately blocks rNav1.1/SCN1A, rNav1.2/SCN2A, rNav1.3/SCN3A, mNav1.6/SCN8A, and h/rNav1.7/SCN9A. This inhibition is reversible. The block of SCN1A, SCN2A, and SCN8A is modified when beta-subunits are coexpressed with alpha subunits. Hence, blocks of channels containing the beta-1 and beta-3 subunits are more potent (compared to channels without beta subunits), whereas blocks of channels containing the beta-2 and beta-4 are less potent (compared to channels without beta subunits). This peptide causes flaccid paralysis in both mice and fish.[1] [2] [3] [4] [5] Publication Abstract from PubMedMu-conotoxins are peptide inhibitors of voltage-sensitive sodium channels (VSSCs). Synthetic forms of mu-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 mu-conotoxins 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. (1)H 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 mu-conotoxins GIIIA and GIIIB that selectively target TTX-sensitive muscle VSSCs. Comparison of the structures and activity of PIIIA to muscle-selective mu-conotoxins provides an insight into the structural requirements for inhibition of different TTX-sensitive sodium channels by mu-conotoxins. Solution structure of mu-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels.,Nielsen KJ, Watson M, Adams DJ, Hammarstrom AK, Gage PW, Hill JM, Craik DJ, Thomas L, Adams D, Alewood PF, Lewis RJ J Biol Chem. 2002 Jul 26;277(30):27247-55. Epub 2002 May 2. PMID:12006587[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Conus purpurascens | Large Structures | Adams D | Adams DJ | Alewood PF | Craik DJ | Gage PW | Hammarstrom AK | Hill JM | Lewis RJ | Nielsen KJ | Thomas L | Watson M
