Distinct primary structures of the major peptide toxins from the venom of the spider Macrothele gigas that bind to sites 3 and 4 in the sodium channel
Distinct primary structures of the major peptide toxins from the venom of the spider Macrothele gigas that bind to sites 3 and 4 in the sodium channel
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DOI：
10.1016/s0014-5793(03)00666-5
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发表时间：
2003-07-17
期刊：
影响因子：
3.5
通讯作者：
Haupt, J
中科院分区：
文献类型：
--
作者：
Corzo, G;Gilles, N;Haupt, J
从大疣蛛（Macrothelegigas）中分离到6种肽毒素（Magi 1-6）。Magi 1、2、5和6的氨基酸序列与已知蜘蛛毒素的氨基酸序列具有低相似性。Magi 3的一级结构类似于来自北美蜘蛛Plectreurys tristis（Plectreuridae）的棕榈酰化肽P1 Tx-II的结构。此外，通过克隆其cDNA揭示的Magi 4的氨基酸序列显示出与来自澳大利亚蜘蛛Atrax rohustus（Hexathelidae）的Na+通道修饰剂δ-肉毒毒素的相似性。使用几种I-125标记的肽毒素的竞争性结合测定清楚地证明了Magi 1-5对昆虫钠通道的位点3的特异性结合亲和力，以及Magi 5对大鼠钠通道的位点4的特异性结合亲和力。只有Magi 6不与蝎毒素LqhalphaIT竞争结合位点3，尽管对鳞翅目幼虫的毒性为3.1 nmol/g。其他毒素的K（i）s在Magi 4的50 pM和Magi 1的1747 nM之间。此外，仅Magi 5结合昆虫中的位点3（Ki = 267 nM）和大鼠脑突触体中的位点4（Ki = 1.2 nM），而它对哺乳动物结合位点3或昆虫结合位点4均不显示亲和力。Magi 5是第一种对哺乳动物钠通道位点4具有结合亲和力的蜘蛛毒素。(C)2003年由Elsevier Science B. V.代表欧洲生物化学学会联合会出版。
Six peptide toxins (Magi 1-6) were isolated from the Hexathelidae spider Macrothele gigas. The amino acid sequences of Magi 1, 2, 5 and 6 have low similarities to the amino acid sequences of known spider toxins. The primary structure of Magi 3 is similar to the structure of the palmitoylated peptide named P1Tx-II from the North American spider Plectreurys tristis (Plectreuridae). Moreover, the amino acid sequence of Magi 4, which was revealed by cloning of its cDNA, displays similarities to the Na+ channel modifier delta-atracotoxin from the Australian spider Atrax rohustus (Hexathelidae). Competitive binding assays using several I-125-labelled peptide toxins clearly demonstrated the specific binding affinity of Magi 1-5 to site 3 of the insect sodium channel and also that of Magi 5 to site 4 of the rat sodium channel. Only Magi 6 did not compete with the scorpion toxin LqhalphaIT in binding to site 3 despite high toxicity on lepidoptera larvae of 3.1 nmol/g. The K(i)s of other toxins were between 50 pM for Magi 4 and 1747 nM for Magi 1. In addition, only Magi 5 binds to both site 3 in insects (K-i = 267 nM) and site 4 in rat brain synaptosomes (K-i = 1.2 nM), whereas it showed no affinities for either mammal binding site 3 or insect binding site 4. Magi 5 is the first spider toxin with binding affinity to site 4 of a mammalian sodium channel. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.