Interaction of an esophageal MEG protein from schistosomes with a human S100 protein involved in inflammatory response.
Interaction of an esophageal MEG protein from schistosomes with a human S100 protein involved in inflammatory response.
复制标题
DOI：
10.1016/j.bbagen.2016.09.015
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
D. Orcia;A. E. Zeraik;J. Lopes;J. N. Macêdo;C. Santos;K. C. Oliveira;Letícia Anderson;B. Wallace;S. Verjovski-Almeida;A. P. Araujo;R. DeMarco
中科院分区：
文献类型：
--
作者：
D. Orcia;A. E. Zeraik;J. Lopes;J. N. Macêdo;C. Santos;K. C. Oliveira;Letícia Anderson;B. Wallace;S. Verjovski-Almeida;A. P. Araujo;R. DeMarco
研究背景血吸虫微外显子基因14（Micro-Exon Gene-14，MEG-14）是血吸虫抗原变异的重要基因。先前的研究表明，MEG-14蛋白的可溶性部分显示出固有无序蛋白的特征，并且仅在寄生虫食管腺中表达。这些功能表明了潜在的相互作用与宿主蛋白质存在于血浆和细胞从摄入blood.MethodsA酵母双杂交实验作为诱饵的曼氏血吸虫MEG-14（sMEG-14）对人类白细胞cDNA文库的可溶性结构域进行。使用下拉和表面等离子体共振（SPR）实验来验证sMEG-14与人S100 A9之间的相互作用。使用同步辐射圆二色性（SRCD）检测sMEG-14与人S100 A9之间相互作用后的结构变化。结果在酵母双杂交、pull-down和SPR实验中，S100 A9与sMEG-14的相互作用一致。SRCD表明，MEG-14由于与S100 A9的相互作用而获得了更规则的结构。结论S100 A9蛋白与sMEG-14蛋白相互作用，提示S100 A9蛋白可能参与了疟原虫的炎症反应，并可能通过抑制MEG-14的表达而抑制炎症反应。当摄入的血细胞溶解时，S100 A9释放时会发生这种情况。
BackgroundThe Micro-Exon Gene-14 (MEG-14) displays a remarkable structure that allows the generation of antigenic variation in Schistosomes. Previous studies showed that the soluble portion of the MEG-14 protein displays features of an intrinsically disordered protein and is expressed exclusively in the parasite esophageal gland. These features indicated a potential for interaction with host proteins present in the plasma and cells from ingested blood.MethodsA yeast two-hybrid experiment using as bait the soluble domain of Schistosoma mansoni MEG-14 (sMEG-14) against a human leukocyte cDNA library was performed. Pull-down and surface plasmon resonance (SPR) experiments were used to validate the interaction between sMEG-14 and human S100A9. Synchrotron radiation circular dichroism (SRCD) were used to detect structural changes upon interaction between sMEG-14 and human S100A9. Feeding of live parasites with S100A9 attached to a fluorophore allowed the tracking of the fate of this protein in the parasite digestive system.ResultsS100A9 interacted with sMEG-14 consistently in yeast two-hybrid assay, pull-down and SPR experiments. SRCD suggested that MEG-14 acquired a more regular structure as a result of the interaction with S100A9. Accumulation of recombinant S100A9 in the parasite's esophageal gland, when ingested by live worms suggests that such interaction may occurin vivo.ConclusionS100A9, a protein previously described to be involved in modulation of inflammatory response, was found to interact with sMEG-14.General significanceOur results allow proposing a mechanism involving MEG-14 for the parasite to block inflammatory signaling, which would occur upon release of S100A9 when ingested blood cells are lysed.