Conotoxin TVIIA, a novel peptide from the venom of Conus tulipa 1. Isolation, characterization and chemical synthesis.
A novel conotoxin belonging to the 'four-loop' structural class has been isolated from the venom of the piscivorous cone snail Conus tulipa. It was identified using a chemical-directed strategy based largely on mass spectrometric techniques. The new toxin, conotoxin TVIIA, consists of 30 amino-acid residues and contains three disulfide bonds. The amino-acid sequence was determined by Edman analysis as SCSGRDSRCOOVCCMGLMCSRGKCVSIYGE where O = 4-transL-hydroxyproline. Two under-hydroxylated analogues, [Pro10]TVIIA and [Pro10,11]TVIIA, were also identified in the venom of C. tulipa. The sequences of TVIIA and [Pro10]TVIIA were further verified by chemical synthesis and coelution studies with native material. Conotoxin TVIIA has a six cysteine/four-loop structural framework common to many peptides from Conus venoms including the omega-, delta- and kappa-conotoxins. However, TVIIA displays little sequence homology with these well-characterized pharmacological classes of peptides, but displays striking sequence homology with conotoxin GS, a peptide from Conus geographus that blocks skeletal muscle sodium channels. These new toxins and GS share several biochemical features and represent a distinct subgroup of the four-loop conotoxins.
Hill
J M
JM
Centre for Drug Design and Development, The Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Atkins
A R
AR
Loughnan
M L
ML
Jones
A
A
Adams
D A
DA
Martin
R C
RC
Lewis
R J
RJ
Craik
D J
DJ
Alewood
P F
PF
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification; D011036:Poecilia; D011485:Protein Binding; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012908:Snails / Q000737:chemistry*
D000596:Amino Acids; D008978:Mollusk Venoms; D010455:Peptides; C413603:conotoxin TVIIA