NMR sequential assignments and solution structure of chlorotoxin, a small scorpion toxin that blocks chloride channels.

TitleNMR sequential assignments and solution structure of chlorotoxin, a small scorpion toxin that blocks chloride channels.
Publication TypeJournal Article
Year of Publication1995
AuthorsLippens, G., Najib J., Wodak S. J., and Tartar A.
JournalBiochemistry
Volume34
Issue1
Pagination13-21
Date Published1995 Jan 10
ISSN0006-2960
KeywordsAmino Acid Sequence, Disulfides, Electrochemistry, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Sequence Data, Neurotoxins, Protein Structure, Secondary, Scorpion Venoms, Sequence Homology, Amino Acid, Solutions, Structure-Activity Relationship
Abstract

The solution structure of chlorotoxin, a small toxin purified from the venom of the Leiurus quinquestriatus scorpion, has been determined using 2D 1H NMR spectroscopy. Analysis of the NMR data shows that the structure consists of a small three-stranded antiparallel beta-sheet packed against an alpha-helix, thereby adopting the same fold as charybdotoxin and other members of the short scorpion toxin family [Arseniev et al. (1984) FEBS Lett. 165, 57-62; Martins et al. (1990) FEBS Lett. 260, 249-253; Bontems et al. (1991) Science 254, 1521-1523]. Three disulfide bonds of chlorotoxin (Cys5-Cys28, Cys16-Cys33, and Cys20-Cys35), cross-linking the alpha-helix to the beta-sheet, follow the common pattern found in the other short scorpion toxins. The fourth disulfide bridge (Cys2-Cys19) links the small N-terminal beta strand to the rest of the molecule, in contrast to charybdotoxin where this disulfide bridge is absent and the first strand interacts with the rest of the molecule by several contacts between hydrophobic residues. Another structural difference between chlorotoxin and charybdotoxin is observed at the level of the alpha-beta turn. This difference is accompanied by a change in the electrostatic potential surface, which is largely positive at the level of this turn in chlorotoxin, whereas no such positive potential surface can be found at the same position in charybdotoxin. In the latter protein, the positive surface is formed by different charged residues situated on the solvent-exposed site of the C-terminal beta-sheet.(ABSTRACT TRUNCATED AT 250 WORDS)

Alternate JournalBiochemistry
PubMed ID7819188