Bisphenol A (BPA) binding on full‐length architectures of estrogen receptor. Issue 8 (8th May 2018)

• Record Type: Journal Article
• Authors: Liu, Yaquan; Qu, Kaili; Hai, Ying; Zhao, Chunyan
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 8(2018)
• Page Start: 6784
• Page End: 6794
• Publication Date: 2018-05-08
• Subjects: bisphenol A (BPA) -- estrogen receptor -- full‐length architectures -- molecular modeling; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26872
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Previous research has shown that the major toxicity mechanism for many environment chemicals is binding with estrogen receptor (ER) and blocking endogenous estrogen access, including bisphenol A (BPA). However, the molecular level understanding the global consequence of BPA binding on the full‐length architectures of ER is largely unknown, which is a necessary stage to evaluate estrogen‐like toxicity of BPA. In the present work, the consequence of BPA on full‐length architectures of ER was firstly modeled based on molecular dynamics, focusing on the cross communication between multi‐domains including ligand binding domain (LBD) and DNA binding domain (DBD). The study proved consequence of BPA upon full‐length ER structure was dependent on long‐range communications between multiple protein domains. The allosteric effects occurring in LBD units could alter dimerization formation through a crucial change in residue‐residue connections, which resulted in relaxation of DBD. It indicated BPA could present consequence on the full‐size receptor, not only on the separate domains, but also on the cross communication among LBD, DBD, and DNA molecules. It might provide detailed insight into the knowledge about the structural characteristics of ER and its role in gene regulation, which eventually helped us evaluate the estrogen‐like toxicity upon BPA binding with full‐length ER. Abstract : A full‐length architectures of estrogen receptor (alpha)‐BPA complex was constructed in the first time, aiming to explore the global consequences of BPA acting. we observed that BPA binding had long‐range effects on the dynamics of the multi‐domains in a precise global conformation, including ligand binding domain (LBD)‐LBD dimerization interfaces, LBD‐DBD (DNA binding domain) interface, and LBD‐DNA interface. The present study might provide ever more clear and detailed insight into the structural consequence and molecular mechanisms of signals transduction in the full‐length ER settings based on BPA‐binding.