PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function

• Published in: Nature chemical biology Vol. 16; no. 8; pp. 876 - 886
• Main Authors: Rajan, Sreekanth, Jang, Yongwoo, Kim, Chun-Hyung, Kim, Woori, Toh, Hui Ting, Jeon, Jeha, Song, Bin, Serra, Aida, Lescar, Julien, Yoo, Jun Yeob, Beldar, Serap, Ye, Hong, Kang, Congbao, Liu, Xue-Wei, Feitosa, Melissa, Kim, Yeahan, Hwang, Dabin, Goh, Geraldine, Lim, Kah-Leong, Park, Hye Min, Lee, Choong Hwan, Oh, Sungwhan F., Petsko, Gregory A., Yoon, Ho Sup, Kim, Kwang-Soo
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2020; Nature Publishing Group
• Subjects: 631/378; 631/92; 631/92/287; 631/92/612/822; Alprostadil - metabolism; Animal models; Animals; Binding; Biochemical Engineering; Biochemistry; Bioorganic Chemistry; Cell Biology; Cell Line, Tumor; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Crystal structure; Crystallography; Crystallography, X-Ray; Dehydration; Domains; Dopamine - metabolism; Dopamine receptors; Gene expression; Genes; Humans; Ligands; Male; Mesencephalon; Metabolites; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Movement disorders; MPTP; Neurodegenerative diseases; Neurons; Neurons - metabolism; Neuroprotection; Neuroprotective Agents - pharmacology; Nuclear Receptor Subfamily 4, Group A, Member 2 - chemistry; Nuclear Receptor Subfamily 4, Group A, Member 2 - genetics; Nuclear Receptor Subfamily 4, Group A, Member 2 - metabolism; Nuclear receptors; Nurr1 protein; Parkinson's disease; Prostaglandin E1; Prostaglandins; Prostaglandins A - metabolism; Protein Binding; Rats; Signal Transduction; Transcription activation; Transcription, Genetic

The orphan nuclear receptor Nurr1 is critical for the development, maintenance and protection of midbrain dopaminergic (mDA) neurons. Here we show that prostaglandin E1 (PGE1) and its dehydrated metabolite, PGA1, directly interact with the ligand-binding domain (LBD) of Nurr1 and stimulate its trans...