Conorfamide-Sr2, a gamma-carboxyglutamate-containing FMRFamide-related peptide from the venom of Conus spurius with activity in mice and mollusks.
A novel peptide, conorfamide-Sr2 (CNF-Sr2), was purified from the venom extract of Conus spurius, collected in the Caribbean Sea off the Yucatan Peninsula. Its primary structure was determined by automated Edman degradation and amino acid analysis, and confirmed by electrospray ionization mass spectrometry. Conorfamide-Sr2 contains 12 amino acids and no Cys residues, and it is only the second FMRFamide-related peptide isolated from a venom. Its primary structure GPM gammaDPLgammaIIRI-nh2, (gamma, gamma-carboxyglutamate; -nh2, amidated C-terminus; calculated monoisotopic mass, 1468.72Da; experimental monoisotopic mass, 1468.70Da) shows two features that are unusual among FMRFamide-related peptides (FaRPs, also known as RFamide peptides), namely the novel presence of gamma-carboxyglutamate, and a rather uncommon C-terminal residue, Ile. CNF-Sr2 exhibits paralytic activity in the limpet Patella opea and causes hyperactivity in the freshwater snail Pomacea paludosa and in the mouse. The sequence similarities of CNF-Sr2 with FaRPs from marine and freshwater mollusks and mice might explain its biological effects in these organisms. It also resembles FaRPs from polychaetes (the prey of C. spurius), which suggests a natural biological role. Based on these similarities, CNF-Sr2 might interact with receptors of these three distinct types of FaRPs, G-protein-coupled receptors, Na+ channels activated by FMRFamide (FaNaCs), and acid-sensing ion channels (ASICs). The biological activities of CNF-Sr2 in mollusks and mice make it a potential tool to study molecular targets in these and other organisms.
Aguilar
Manuel B
MB
Laboratorio de Neurofarmacología Marina, Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro 76230, Mexico. maguilar@servidor.unam.mx
Luna-Ramírez
Karen S
KS
Echeverría
Daniel
D
Falcón
Andrés
A
Olivera
Baldomero M
BM
Heimer de la Cotera
Edgar P
EP
Maillo
María
M
D015055:1-Carboxyglutamic Acid / Q000737:chemistry*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology; D052078:Conus Snail / Q000737:chemistry*; D019835:FMRFamide / Q000737:chemistry*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D008974:Mollusca; D008978:Mollusk Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011036:Poecilia; D020539:Sequence Analysis, Protein; D012908:Snails
D000596:Amino Acids; D008978:Mollusk Venoms; D009479:Neuropeptides; D010455:Peptides; C529126:conorfamide-Sr2, Conus spurius; D015055:1-Carboxyglutamic Acid; D019835:FMRFamide