Characterization of the Estradiol-Binding Site Structure of Human   Protein Disulfide Isomerase (PDI)

doi:10.1371/journal.pone.0027185

CORC > 北京大学 > 生命科学学院

	Characterization of the Estradiol-Binding Site Structure of Human Protein Disulfide Isomerase (PDI)
	Fu, Xin-Miao ; Wang, Pan ; Zhu, Bao Ting
刊名	plos one
	2011
关键词	ENDOPLASMIC-RETICULUM TARGET-CELLS ESTROGEN-RECEPTOR HORMONE-BINDING HIV-1 ENTRY INHIBITORS GLYCOPROTEIN-120 CHAPERONE DOMAIN BONDS
DOI	10.1371/journal.pone.0027185
英文摘要	Background: Earlier studies showed that 17 beta-estradiol (E-2), an endogenous female sex hormone, can bind to human protein disulfide isomerase (PDI), a protein folding catalyst for disulfide bond formation and rearrangement. This binding interaction can modulate the intracellular levels of E-2 and its biological actions. However, the structure of PDI's E-2-binding site is still unclear at present, which is the focus of this study. Methodology/Principal Findings: The E-2-binding site structure of human PDI was studied by using various biochemical approaches coupled with radiometric receptor-binding assays, site-directed mutagenesis, and molecular computational modeling. Analysis of various PDI protein fragments showed that the [H-3]E-2-binding activity is not associated with the single b or b' domain but is associated with the b-b' domain combination. Computational docking analyses predicted that the E-2-binding site is located in a hydrophobic pocket composed mainly of the b' domain and partially of the b domain. A hydrogen bond, formed between the 3-hydroxyl group of E-2 and His256 of PDI is critical for the binding interaction. This binding model was jointly confirmed by a series of detailed experiments, including site-directed mutagenesis of the His256 residue coupled with selective modifications of the ligand structures to alter the binding interaction. Conclusions/Significance: The results of this study elucidated the structural basis for the PDI-E-2 binding interaction and the reservoir role of PDI in modulating the intracellular E-2 levels. The identified PDI E-2-binding site is quite different from its known peptide binding sites. Given that PDI is a potential therapeutic target for cancer chemotherapy and HIV prevention and that E-2 can inhibit PDI activity in vitro, the E-2-binding site structure of human PDI determined here offers structural insights which may aid in the rational design of novel PDI inhibitors.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000297197000030&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Multidisciplinary Sciences; SCI(E); 6; ARTICLE; 11; 6
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/394132]
专题	生命科学学院
推荐引用方式 GB/T 7714	Fu, Xin-Miao,Wang, Pan,Zhu, Bao Ting. Characterization of the Estradiol-Binding Site Structure of Human Protein Disulfide Isomerase (PDI)[J]. plos one,2011.
APA	Fu, Xin-Miao,Wang, Pan,&Zhu, Bao Ting.(2011).Characterization of the Estradiol-Binding Site Structure of Human Protein Disulfide Isomerase (PDI).plos one.
MLA	Fu, Xin-Miao,et al."Characterization of the Estradiol-Binding Site Structure of Human Protein Disulfide Isomerase (PDI)".plos one (2011).