A conotoxin from Conus textile with unusual posttranslational modifications reduces presynaptic Ca2+ influx

被引:112
作者
Rigby, AC
Lucas-Meunier, E
Kalume, DE
Czerwiec, E
Hambe, B
Dahlqvist, I
Fossier, P
Baux, G
Roepstorff, P
Baleja, JD
Furie, BC
Furie, B
Stenflo, J [1 ]
机构
[1] Marine Biol Lab, Woods Hole, MA 02543 USA
[2] Harvard Univ, Sch Med, Ctr Hemostasis & Thrombosis Res, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
[3] Univ Lund Hosp, Dept Clin Chem, S-20502 Malmo, Sweden
[4] CNRS, Neurobiol Cellulaire & Mol Lab, F-91198 Gif Sur Yvette, France
[5] Odense Univ, Dept Mol Biol, DK-5230 Odense M, Denmark
[6] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA
关键词
D O I
10.1073/pnas.96.10.5758
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cone snails are gastropod mollusks of the genus Conus that live in tropical marine habitats. They are predators that paralyze their prey by injection of venom containing a plethora of small, conformationally constrained peptides (conotoxins), We report the identification, characterization, and structure of a gamma-carboxyglutamic acid-containing peptide, conotoxin epsilon-TxIX, isolated from the venom of the molluscivorous cone snail, Conus textile. The disulfide bonding pattern of the four cysteine residues, an unparalleled degree of posttranslational processing including bromination, hydroxylation, and glycosylation define a family of conotoxins that may target presynaptic Ca2+ channels or act on G protein-coupled presynaptic receptors via another mechanism. This conotoxin selectively reduces neurotransmitter release at an Aplysia cholinergic synapse by reducing the presynaptic influx of Ca2+ in a slow and reversible fashion, The three-dimensional structure, determined by two-dimensional H-1 NMR spectroscopy, identifies an electronegative patch created by the side chains of two gamma-carboxyglutamic acid residues that extend outward from a cavernous cleft. The glycosylated threonine and hydroxylated proline enclose a localized hydrophobic region centered on the brominated tryptophan residue within the constrained intercysteine region.
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收藏
页码:5758 / 5763
页数:6
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