biosensors paving the way to understanding the interaction between cadmium and the estrogen receptor alpha生物传感器铺平了道路理解之间的交互镉和雌激素受体α.pdf

Biosensors Paving the Way to Understanding the Interaction between Cadmium and the Estrogen Receptor Alpha 1 2 ¨ 1 Peter Fechner , Pauliina Damdimopoulou , Gunter Gauglitz * ¨ ¨ 1 Institute of Physical and Theoretical Chemistry (IPTC), Eberhard-Karls-University of Tubingen, Tubingen, Germany, 2 Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden Abstract Cadmium is a toxic heavy metal ubiquitously present in the environment and subsequently in the human diet. Cadmium has been proposed to disrupt the endocrine system, targeting in particular the estrogen signaling pathway already at environmentally relevant concentrations. Thus far, the reports on the binding affinity of cadmium towards human estrogen receptor alpha (hERa) have been contradicting, as have been the reports on the in vivo estrogenicity of cadmium. Hence, the mode of interaction between cadmium and the receptor remains unclear. Here, we investigated the interaction between cadmium and hERa on a molecular level by applying a novel, label-free biosensor technique based on reflectometric interference spectroscopy (RIfS). We studied the binding of cadmium to hERa, and the conformation of the receptor following cadmium treatment. Our data reveals that cadmium interacts with the ligand binding domain (LBD) of the ERa and affects the conformation of the receptor. However, the binding event, as well as the induced conformation change, greatly depends on the accessibility of the cysteine tails in the LBD. As the LBD cysteine residues have been reported as targets of post-translational modifications in vivo, we present a hypothesis acc