Novel excitatory Conus peptides define a new conotoxin superfamily

Autor: Jean Rivier, Doju Yoshikami, Craig S. Walker, Baldomero M. Olivera, Lourdes J. Cruz, Marcelina B. Lirazan, Reshma Shetty, Fe C. Abogadie, Elsie C. Jimenez
Rok vydání: 2003
Předmět:
Zdroj: Journal of Neurochemistry. 85:610-621
ISSN: 1471-4159
0022-3042
DOI: 10.1046/j.1471-4159.2003.01685.x
Popis: A new class of Conus peptides, the I-superfamily of conotoxins, has been characterized using biochemical, electrophysiological and molecular genetic methods. Peptides in this superfamily have a novel pattern of eight Cys residues. Five peptides that elicited excitatory symptomatology, r11a, r11b, r11c, r11d and r11e, were purified from Conus radiatus venom; four were tested on amphibian peripheral axons and shown to elicit repetitive action potentials, consistent with being members of the 'lightning-strike cabal' of toxins that effect instant immobilization of fish prey. A parallel analysis of Conus cDNA clones revealed a new class of conotoxin genes that was particularly enriched (with 18 identified paralogues) in a Conus radiatus venom duct library; several C. radiatus clones encoded the excitatory peptides directly characterized from venom. The remarkable diversity of related I-superfamily peptides within a single Conus species is unprecedented. When combined with the excitatory effects observed on peripheral circuitry, this unexpected diversity suggests a corresponding molecular complexity of the targeted signaling components in peripheral axons; the I-conotoxin superfamily should provide a rich lode of pharmacological tools for dissecting and understanding these. Thus, the I-superfamily conotoxins promise to provide a significant new technology platform for dissecting the molecular components of axons.
Databáze: OpenAIRE