Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.
Environ Sci Technol. 2024 Sep 10;58(36):15960-15970. doi: 10.1021/acs.est.4c03648. Epub 2024 Aug 29.
Fresh water sources, including lakes, such as the Great Lakes, are some of the most important ecosystems in the world. Despite the importance of these lakes, there is increasing concern about the presence of per- and polyfluoroalkyl substances (PFAS)─among the most prevalent contaminants of our time─due to the ability of PFAS to bioaccumulate and persist in the environment, as well as to its linkages to detrimental human and animal health effects. In this study, PFAS exposure on rainbow trout () is examined at the molecular level, focusing on the impact of PFAS binding on the alpha (α) and beta (β) estrogen receptors (ERs) using molecular dynamics simulations, binding free energy calculations, and structural analysis. ERs are involved in fundamental physiological processes, including reproductive system development, muscle regeneration, and immunity. This study shows that PFAS binds to both the estrogen α and estrogen β receptors, albeit via different binding modes, due to a modification of an amino acid in the binding site as a result of a reorientation of residues in the binding pocket. As ER overactivation can occur through environmental toxins and pollutants, this study provides insights into the influence of different types of PFAS on protein function.
淡水来源，包括湖泊，如五大湖，是世界上最重要的生态系统之一。尽管这些湖泊非常重要，但由于全氟和多氟烷基物质（PFAS）能够在环境中生物积累和持久存在，以及与人类和动物健康有害影响的关联，人们越来越关注 PFAS 的存在，PFAS 是目前最普遍的污染物之一。在这项研究中，从分子水平上研究了虹鳟鱼中的 PFAS 暴露情况，重点研究了 PFAS 结合对 alpha (α) 和 beta (β) 雌激素受体 (ER) 的影响，使用了分子动力学模拟、结合自由能计算和结构分析。ER 参与了包括生殖系统发育、肌肉再生和免疫在内的基本生理过程。这项研究表明，PFAS 与雌激素 α 和雌激素 β 受体结合，尽管结合模式不同，这是由于结合位点中的一个氨基酸因结合口袋中残基的重排而发生了修饰。由于 ER 的过度激活可能是由于环境毒素和污染物引起的，因此这项研究提供了对不同类型的 PFAS 对蛋白质功能影响的深入了解。
