a-Conotoxins that target the neuronal nicotinic acetylcho-line receptor have a range of potential therapeutic applica-tions and are valuable probes for examining receptor subtype selectivity. The three-dimensional structures of about half of the knownneuronal specifica-conotoxins have nowbeendeterminedandhaveaconsensus foldcontaininga helical region braced by two conserved disulfide bonds. These disulfide bonds define the two-loop framework char-acteristic for a-conotoxins, CCXmCXnC, where loop 1 comprisesfourresidues(m¼4) and loop 2 between three and seven residues (n¼3, 6 or 7). .