SRC2-3 binds to vitamin D receptor with high sensitivity and strong affinity

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• 作者：Daichi Egawa ; Toshimasa Itoh ; Akira Kato ; Saori Kataoka ; Yasuaki Anami ; Keiko Yamamoto ; ^{yamamoto@ac.shoyaku.ac.jp}
• 关键词：VDR ; vitamin D receptor ; LBD ; ligand-binding domain ; DRIP ; vitamin D receptor interacting protein ; SRC ; steroid receptor coactivator ; SPR ; surface plasmon resonance ; AF2 ; activation-function 2
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：25
• 期：2
• 页码：568-574
• 全文大小：1734 K
• 卷排序：25

文摘

Vitamin D receptor (VDR) is a member of the nuclear receptor superfamily and regulates the expression of target genes through ligand binding. To express the target gene, coactivator binding to the VDR/ligand complex is essential. Although there are many coactivators in living cells, precise interactions between coactivators and VDR have not been clarified. Here, we synthesized two coactivator peptides, DRIP205-2 and SRC2-3, evaluated their affinity for the ligand-binding domain (LBD) of VDR using 1α,25-dihydroxyvitamin D3, partial agonist 1, and antagonist 2 by surface plasmon resonance (SPR), and assessed their interaction modes with VDR-LBD using X-ray crystallographic analysis. This study showed that the SRC2-3 peptide is more sensitive to the ligands (agonist, partial agonist, and antagonist) and shows more intimate interactions with VDR-LBD than DRIP205-2 peptide.