AlphaA-Conotoxin OIVA defines a new alphaA-conotoxin subfamily of nicotinic acetylcholine receptor inhibitors.
The venoms of cone snails are rich in multiply disulfide-crosslinked peptides, the conotoxins. Conotoxins are grouped into families on the basis of shared cysteine patterns and homologous molecular targets. For example, both the kappaA- and alphaA-conotoxin families share the same Class IV Cys pattern (-CC-C-C-C-C-), but differ in their molecular targets. The kappaA-conotoxins are excitatory toxins that purportedly block potassium channels, while the alphaA-conotoxins are paralytic conotoxins that inhibit nicotinic acetylcholine receptors (nAChRs). In this work, we describe the isolation and characterization of a novel Conus peptide from venom milked from Hawaiian specimens of Conus obscurus. This peptide shares the Class IV Cys pattern but differs from both previously characterized alphaA- and kappaA-conotoxins in the spacing of amino acids between Cys resides. However, the peptide is similar to previously characterized alphaA-conotoxins in its paralytic effects on fish and its antagonist activity on the neuromuscular nAChR. Unexpectedly, the peptide differs in its disulfide bonding from alphaA-conotoxin PIVA. We have named this unique peptide alphaA-conotoxin OIVA, and we consider it the defining member of a subfamily of alphaA-conotoxins that we designate the alphaA(1-3)-conotoxins to identify them by their unique disulfide bonding framework. These results indicate that the alphaA-conotoxin family is both more structurally diverse and broadly distributed than previously believed.
Teichert
Russell W
RW
Department of Biology, University of Utah, 254 South 1400 East, Salt Lake City, UT 84112, USA. russ_teichert@yahoo.com
Rivier
Jean
J
Dykert
John
J
Cervini
Laura
L
Gulyas
Jozsef
J
Bulaj
Grzegorz
G
Ellison
Michael
M
Olivera
Baldomero M
BM
D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D020916:Conotoxins / Q000737:chemistry / Q000145:classification / Q000302:isolation & purification* / Q000494:pharmacology; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011487:Protein Conformation; D011978:Receptors, Nicotinic / Q000187:drug effects*; D016415:Sequence Alignment; D012908:Snails
D020916:Conotoxins; D008978:Mollusk Venoms; D018733:Nicotinic Antagonists; D010455:Peptides; D010456:Peptides, Cyclic; D011978:Receptors, Nicotinic; C492637:alphaA-conotoxin OIVA