alpha-Conotoxins, small peptide probes of nicotinic acetylcholine receptors.
alpha-Conotoxins, a family of small peptides from the venoms of the Conus marine moluscs, are selective, snake alpha-neurotoxin-competitive antagonists of the nicotinic acetylcholine receptor. A new alpha-conotoxin, SIA, has been purified, sequenced, and synthesized. Cross-linking with bivalent reagents and photoaffinity labeling of the acetylcholine receptor with alpha-conotoxin yield covalent adducts. Surprisingly, cross-linking to other subunits is considerably more efficient than to the alpha subunit. The relative efficiency of photoactivatable cross-linking to different subunits of the receptor is a function of placement of the photoactivatable group on the toxin. Since the structures of alpha-conotoxins can be solved by 2D NMR [see Pardi et al. (1989) Biochemistry 28, 5494-5508; Kobayashi et al. (1989) Biochemistry 28, 4853-4860], this family of toxins should provide a set of new ligands for probing the acetylcholine receptor with considerable precision.
Myers
R A
RA
Department of Biology, University of Utah, Salt Lake City 84112.
Zafaralla
G C
GC
Gray
W R
WR
Abbott
J
J
Cruz
L J
LJ
Olivera
B M
BM
D000345:Affinity Labels; D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins; D003432:Cross-Linking Reagents; D003902:Detergents; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000187:drug effects*; D012995:Solubility; D013329:Structure-Activity Relationship; D014101:Torpedo
D000345:Affinity Labels; D020916:Conotoxins; D003432:Cross-Linking Reagents; D003902:Detergents; D008978:Mollusk Venoms; D010456:Peptides, Cyclic; D011978:Receptors, Nicotinic; C070987:alpha-conotoxin SIA