PURIFICATION, CHARACTERIZATION, SYNTHESIS, AND CLONING OF THE LOCKJAW PEPTIDE FROM CONUS-PURPURASCENS VENOM

被引:93
作者
SHON, KJ
GRILLEY, MM
MARSH, M
YOSHIKAMI, D
HALL, AR
KURZ, B
GRAY, WR
IMPERIAL, JS
HILLYARD, DR
OLIVERA, BM
机构
[1] UNIV UTAH,DEPT BIOL,SALT LAKE CITY,UT 84112
[2] UNIV UTAH,DEPT PATHOL,SALT LAKE CITY,UT 84112
关键词
D O I
10.1021/bi00015a002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The major groups of Conus peptides previously characterized from fish-hunting cone snail venoms (the alpha-, mu-, and omega-conotoxins) all blocked neuromuscular transmission. A novel activity, the ''lockjaw peptide'', from the fish-hunting Conus purpurascens, caused a rigid (instead of flaccid) paralysis in fish and increased excitability at the neuromuscular junction (instead of a block). We report the purification, biological activity, biochemical and preliminary physiological characterization, and chemical synthesis of the lockjaw peptide and the sequence of a cDNA clone encoding its precursor. Taken together, the data lead us to conclude that the lockjaw peptide is a vertebrate-specific delta-conotoxin, which targets voltage-sensitive sodium channels. The sequence of the peptide, which we designate delta-conotoxin PVIA, is (O = 4-trans-hydroxyproline) EACYAOGTFCGIKOGLCCSEFCLPGVCFG-NH2. This is the first of a diverse spectrum of Conus peptides which are excitotoxins in vertebrate systems.
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页码:4913 / 4918
页数:6
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