赛德罗卡林/菌素相互作用:哺乳动物免疫和细菌铁运输之间的联系
Rebecca J Abergel1, Matthew C Clifton, Juan C Pizarro
1Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Journal of the American Chemical Society
|August 6, 2008
概括
西德罗卡林 (Scn) 隔离细菌肠杆菌 (Ent) 铁复合物. 酸性条件导致铁的释放,降解Ent并改变其协调,影响Scnn.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
背景情况:
- 肠杆菌素 (Ent) 是肠道细菌中铁吸收的 siderophore.
- 赛德罗卡林 (Scn) 是一种免疫蛋白质,可以隔离恩铁复合体,作为抗菌剂.
- 目前正在研究Scn在铁运输和 siderophore 清除中的作用,特别是其在酸性环境中的机制.
研究的目的:
- 为了研究不同pH值的铁性肠杆菌素 ([Fe ((III)) ((Ent)) ((3-)) 和Siderocalin (Scn)) 之间的相互作用.
- 了解Scn突变体与[Fe (III) ] (Ent) 的结构和结合动态.
- 为了阐明在酸性条件下从Scn结合的 siderophores释放铁的机制.
主要方法:
- 对突变的Scn蛋白 (Scn-W79A/R81A和Scn-Y106F) 的制备和结构分析.
- 使用光,UV-vis和EXAFS光谱仪进行约束性研究.
- 对Scn/siderophore解离常数和铁协调的pH依赖分析.
主要成果:
- 突变的Scn蛋白质对[Fe (III) (Ent) ]的亲和力降低,但没有改变整体蛋白质构造.
- 结合scn抑制了En的pH依赖的协调变化,即从catecholate转变为salicylate.
- 强烈的酸化导致铁的释放和Ent的降解,有证据表明这两种机制都有助于铁的释放.
结论:
- 酸性内分泌体中从Scn结合的菌素中释放的铁,很可能是由Ent降解和改变铁协调的组合介导的.
- 鉴于Scn在细胞铁运输中的潜在作用,了解这种机制至关重要.
- 突变性研究提供了关于Scn-siderophore相互作用的结构基础的见解.
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