The structure of a novel insect peptide explains its Ca2+ channel blocking and antifungal activities
The structure of a novel insect peptide explains its Ca2+ channel blocking and antifungal activities
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DOI：
10.1021/bi701319t
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发表时间：
2007-12-04
期刊：
影响因子：
2.9
通讯作者：
Kawano, Keiichi
中科院分区：
文献类型：
--
作者：
Kouno, Takahide;Mizuguchi, Mineyuki;Kawano, Keiichi
滞育特异肽(DSP)是从叶甲虫中提取的一种抑制钙离子通道并具有抗真菌活性的多肽。DSP作用于肾上腺髓质嗜铬细胞的方式类似于omega-conooxin GVIA，GVIA是一种众所周知的神经毒肽，它阻断N型电压依赖性钙通道。然而，DSP的氨基酸序列与任何其他已知的钙通道阻滞剂或抗真菌多肽几乎没有同源性。本文利用二维H-1核磁共振分析了DSP的溶液结构，确定了形成二硫键的半胱氨酸残基的配对。这三个二硫键在DSP中的排列与其他抗真菌多肽和芋螺毒素不同。DSP的整体结构紧凑，部分原因是三个二硫键，有趣的是，它与昆虫和植物来源的抗真菌多肽非常相似。另一方面，DSP和GVIA的二硫键排列和三维结构并不相似。然而，DSP的一些表面残基叠加在GVIA的关键功能残基上。这种疏水侧链和带电侧链的同源分布可能导致了DSP和GVIA之间的功能相似。因此，我们认为，DSP的三维结构可以解释其作为钙通道阻滞剂和抗真菌多肽的双重功能。
Diapause-specific peptide (DSP), derived from the leaf beetle, inhibits Ca2+ channels and has antifungal activity. DSP acts on chromaffin cells of the adrenal medulla in a fashion similar to that of omega-conotoxin GVIA, a well-known neurotoxic peptide, and blocks N-type voltage-dependent Ca2+ Channels. However, the amino acid sequence of DSP has little homology with any other known Ca2+ channel blockers or antifungal peptides. In this paper, we analyzed the solution structure of DSP by using two-dimensional H-1 nuclear magnetic resonance and determined the pairing of half-cystine residues forming disulfide bonds. The arrangement of the three disulfide bridges in DSP was distinct from that of other antifungai peptides and conotoxins. The overall structure of DSP is compact due in part to the three disulfide bridges and, interestingly, is very similar to those of the insect- and plant-derived antifungal peptides. On the other hand, the disulfide arrangement and the three-dimensional structure of DSP and GVIA are not similar. Nevertheless, some surface residues of DSP superimpose on the key functional residues of GVIA. This homologous distribution of hydrophobic and charged side chains may result in the functional similarity between DSP and GVIA. Thus, we propose here that the three-dimensional structure of DSP can explain its dual function as a Ca2+ channel blocker and antifungal peptide.