Peptides From Conus Venoms Which Affects Ca** Entry Into Neurons

Baldomero  M. Olivera,; Jean  Rivier,; Cruz  J. Lourdes,; Julie  A. Haack,; Richard  A. Myers,; J. Michael  Mcintosh,; Julita  Imperial,; Robert  W. Williams,; Terry  Oas,; Jean Francois  Hernandez,

Peptides From Conus Venoms Which Affects Ca** Entry Into Neurons

Abstract:

The venoms of fish-hunting Conus contain paralytic conotoxins and an unprecedented variety of other biologically-active peptides. Particularly noteworthy are peptides which inhibit calcium entry into neurons, The conantokins and w-conotoxins which target NMDA receptors and voltage-sensitive Ca channels respectively. The conantokins contain at least four residues of y-carboxyglutamate (Gla), a post-translationally modified amino acid. Conantokins are folded an a-helical conformation and bind acidic membranes in a calcium-dependent manner. Upon envenomation, conantokins may concentrate on appropriate membranes and target to peripheral fish NMDA receptors located on such membranes. The w-conotoxins are disulfied bonded peptides; a comparison of several w-conotoxins sequences reveals considerable sequence variability. Recent studies with w-conotoxins have also revealed a developmental specificity in mice. The results suggest that elements controlling breathing in neonatal mammals, but not in adults, are w-conotoxin sensitive.