δ/ω-Plectoxin-Pt1a: an excitatory spider toxin with actions on both Ca(2+) and Na(+) channels.

δ/ω-Plectoxin-Pt1a: an excitatory spider toxin with actions on both Ca(2+) and Na(+) channels.
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DOI:
10.1371/journal.pone.0064324
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Branton WD
Branton WD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhou Y;Zhao M;Fields GB;Wu CF;Branton WD

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蜘蛛的毒液含有多种肽毒素,选择性地靶向神经元离子通道。苏氨酸或丝氨酸残基的O-棕榈酰化,沿着特征性的高度受限的二硫键结构,是在这种毒液中发现的毒素家族的标志。在这里,我们报告了一个新的毒素,δ/ω-plectoxin-Pt 1a,从这种蜘蛛毒液的分离和表征。它是含有O-棕榈酰化Ser-39的40个氨基酸肽。对δ/ω-plectoxin-Pt 1a cDNA的分析揭示了一个含有分泌信号序列、一个14个氨基酸的N-末端前肽和一个C-末端酰胺化信号的小前体。δ/ω-plectoxin-Pt 1a的生物活性也是独特的。它优先阻断神经递质释放显然不需要的Ca 2+通道子集;降低Na+通道激活阈值;并减缓Na+通道失活。δ/ω-plectoxin-Pt 1a通过延长突触前神经递质的释放而增强突触传递,其对Na+和Ca ~(2+)通道的作用可能协同维持终末兴奋性。
The venom of spider Plectreurys tristis contains a variety of peptide toxins that selectively target neuronal ion channels. O-palmitoylation of a threonine or serine residue, along with a characteristic and highly constrained disulfide bond structure, are hallmarks of a family of toxins found in this venom. Here, we report the isolation and characterization of a new toxin, δ/ω-plectoxin-Pt1a, from this spider venom. It is a 40 amino acid peptide containing an O-palmitoylated Ser-39. Analysis of δ/ω-plectoxin-Pt1a cDNA reveals a small precursor containing a secretion signal sequence, a 14 amino acid N-terminal propeptide, and a C-terminal amidation signal. The biological activity of δ/ω-plectoxin-Pt1a is also unique. It preferentially blocks a subset of Ca2+ channels that is apparently not required for neurotransmitter release; decreases threshold for Na+ channel activation; and slows Na+ channel inactivation. As δ/ω-plectoxin-Pt1a enhances synaptic transmission by prolonging presynaptic release of neurotransmitter, its effects on Na+ and Ca2+ channels may act synergistically to sustain the terminal excitability.
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