Gao Bin, Rodriguez Maria del Carmen, Lanz-Mendoza Humberto, Zhu Shunyi
Group of Animal Innate Immunity, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
Biochem Biophys Res Commun. 2009 Sep 18;387(2):393-8. doi: 10.1016/j.bbrc.2009.07.043. Epub 2009 Jul 15.
Antimicrobial defensins with the cysteine-stabilized alpha-helical and beta-sheet (CSalphabeta) motif are widely distributed in three eukaryotic kingdoms. However, recent work suggests that bacteria could possess defensin-like peptides (DLPs). Here, we report recombinant expression, in vitro folding, structural and functional characterization of a DLP from the myxobacterium Anaeromyxobacter dehalogenans (AdDLP). Circular dichroism analysis indicates that recombinant AdDLP adopts a typical structural feature of eukaryotic defensins, which is also consistent with an ab initio structure model predicted using I-TASSER algorithm. We found that AdDLP is an antimalarial peptide that led to more than 50% growth inhibition on sexual stages of Plasmodium berghei at micromolar concentrations and killed 100% intraerythrocytic Plasmodium falciparum at 10 microM in a time-dependent manner. These results provide functional evidence for myxobacterial origin of eukaryotic defensins. High-level production of the pure anti-Plasmodium peptide without harming mammalian red blood cells in Escherichia coli makes AdDLP an interesting candidate for antimalarial drug design.
具有半胱氨酸稳定的α-螺旋和β-折叠（CSαβ）基序的抗菌防御素广泛分布于三个真核生物界。然而，最近的研究表明细菌可能拥有防御素样肽（DLP）。在此，我们报告了来自粘细菌脱卤厌氧粘细菌（AdDLP）的一种DLP的重组表达、体外折叠、结构和功能表征。圆二色性分析表明，重组AdDLP具有真核防御素的典型结构特征，这也与使用I-TASSER算法预测的从头结构模型一致。我们发现AdDLP是一种抗疟肽，在微摩尔浓度下对伯氏疟原虫的有性阶段导致超过50%的生长抑制，并在10微摩尔浓度下以时间依赖性方式杀死100%的红细胞内恶性疟原虫。这些结果为真核防御素的粘细菌起源提供了功能证据。在大肠杆菌中高水平生产纯抗疟肽且不损害哺乳动物红细胞，使得AdDLP成为抗疟药物设计的一个有趣候选物。
