广泛的PFAS与脂肪酸结合蛋白4的结合是通过可变的结合方式实现的
Aaron S Birchfield1, Faik N Musayev2,3, Abdul J Castillo1
1Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284, U.S.A.
人类脂肪细胞脂肪酸结合蛋白 (FABP4) 结合了各种和多基物质 (PFAS),包括遗留化学品的替代品. 结构分析揭示了不同的结合模式,影响毒理学结果和代谢调节.
科学领域:
- 环境化学环境化学
- 结构生物学 结构生物学
- 毒理学 毒理学 毒理学
背景情况:
- 和多基基物质 (PFAS) 是已知的广泛存在的环境污染物.
- PFAS与生物蛋白的相互作用背后的分子机制尚不清楚.
- 人体脂肪细胞脂肪酸结合蛋白 (FABP4) 在代谢调节和内分泌功能中起作用.
研究的目的:
- 研究FABP4与多种PFAS之间的结合相互作用.
- 阐明PFAS-FABP4复合体形成的结构基础.
- 了解PFAS与FABP4结合如何影响新陈代谢过程和疾病风险.
主要方法:
- 光竞争试验用于测量结合亲和力.
- 进行X射线晶体学以确定FABP4与特定PFAS (PFOA,PFDA,PFHxDA) 复合的结构.
- 结合模式的分析及其与化学性质的相关性.
主要成果:
- FABP4结合了各种PFAS,包括新的替代物和长链化合物.
- 短链PFAS对FABP4具有可测量的结合亲和力,超过非化类型的PFAS.
- 晶体结构显示了PFOA,PFDA和PFHxDA的三个不同的结合模式,PFOA在两个位点结合.
- 结合模式涉及增强的疏水相互作用和独特的蛋白质构造,解释观察到的亲缘关系.
结论:
- PFAS-FABP4相互作用受到PFAS链长,头组和蛋白质构成的影响.
- 结合FABP4的PFAS,即使在低亲和度,也可能由于FABP4在内分泌功能中的作用扰乱代谢调节.
- 结构和生化洞察力对于理解PFAS运输和毒理影响至关重要.
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