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Bisphenol A (BPA) binding on full‐length architectures of estrogen receptor
Author(s) -
Liu Yaquan,
Qu Kaili,
Hai Ying,
Zhao Chunyan
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26872
Subject(s) - estrogen receptor , allosteric regulation , estrogen receptor alpha , bisphenol a , chemistry , estrogen , molecular dynamics , receptor , binding domain , estrogen receptor beta , small molecule , biophysics , binding site , computational biology , biochemistry , biology , genetics , computational chemistry , organic chemistry , cancer , breast cancer , epoxy
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.