Structural basis of NR4A1 bound to the human pituitary proopiomelanocortin gene promoter

• Published in: Biochemical and biophysical research communications Vol. 523; no. 1; pp. 1 - 5
• Main Authors: Jiang, Longying, Wei, Hudie, Yan, Ningning, Dai, Shuyan, Li, Jun, Qu, Lingzhi, Chen, Xiaojuan, Guo, Ming, Chen, Zhuchu, Chen, Yongheng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.02.2020
• Subjects: Crystal structure; Gene regulation; Nuclear receptor subfamily 4 group A member 1; Nur-responsive elements; Pituitary proopiomelanocortin; Protein-DNA binding; Pituitary proopiomelanocortin; Nur-responsive elements; Protein-DNA binding; Gene regulation; Nuclear receptor subfamily 4 group A member 1; Crystal structure
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.11.192

The nuclear receptor NR4A subfamily (NR4A1/NGFI-B, NR4A2/Nurr1 and NR4A3/NOR-1) can recognize different classes of DNA response elements either as a monomer, homodimer, or heterodimer. In this study, we determined the structure of the NR4A1 DNA-binding domain (NR4A1-DBD) bound to natural Nur-responsive elements (NurREs) in the promoter region of the pituitary proopiomelanocortin (POMC) gene (NurREPOMC) at 3.12 Å resolution. The NR4A1-DBD molecules bound independently to this element in our structure. The N-terminal helix H1 forms specific contacts with major groove, and C-terminal extension interact extensively with minor groove. Moreover our modelling structure of NR4A1 large fragment complexed with NurREPOMC indicated that ligand binding domain of NR4A might form dimer interactions to help recognize DNA. Overall, our analyses provide a molecular basis for DNA binding of NR4A proteins as a homodimer and novel insight into the molecular functions of NR4A modulation of gene expression. •A crystal structure of NR4A1/DNA complexes was solved.•The DNA element is a natural sequence located in the promoter of pituitary proopiomelanocortin (POMC) gene.•A structure of full length NR4A1/DNA complexes was modeled based on our crystal structure.•A dimerization interface might exist in the ligand binding domain in the modeled structure.