6L6Q

Structural basis of NR4A2 homodimers binding to selective Nur-responsive elements

Summary for 6L6Q

• Entry DOI: 10.2210/pdb6l6q/pdb
• Descriptor: Nuclear receptor related 1, DNA (5'-D(P*AP*GP*TP*GP*AP*CP*CP*TP*TP*TP*AP*AP*AP*GP*GP*TP*CP*AP*CP*T)-3'), ZINC ION, ... (4 entities in total)
• Functional Keywords: nr4a2, nuclear receptor, dna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 31920.65

Authors

Jiang, L.,Chen, Y. (deposition date: 2019-10-29, release date: 2019-11-20, Last modification date: 2023-11-22)

Primary citation

Jiang, L.,Dai, S.,Li, J.,Liang, X.,Qu, L.,Chen, X.,Guo, M.,Chen, Z.,Chen, L.,Wei, H.,Chen, Y.
Structural basis of binding of homodimers of the nuclear receptor NR4A2 to selective Nur-responsive DNA elements.
J.Biol.Chem., 294:19795-19803, 2019

PubMed Abstract: Proteins of nuclear receptor subfamily 4 group A (NR4A), including NR4A1/NGFI-B, NR4A2/Nurr1, and NR4A3/NOR-1, are nuclear transcription factors that play important roles in metabolism, apoptosis, and proliferation. NR4A proteins recognize DNA response elements as monomers or dimers to regulate the transcription of a variety of genes involved in multiple biological processes. In this study, we determined two crystal structures of the NR4A2 DNA-binding domain (NR4A2-DBD) bound to two Nur-responsive elements: an inverted repeat and an everted repeat at 2.6-2.8 Å resolution. The structures revealed that two NR4A2-DBD molecules bind independently to the everted repeat, whereas two other NR4A2-DBD molecules form a novel dimer interface on the inverted repeat. Moreover, substitution of the interfacial residue valine 298 to lysine as well as mutation of DNA bases involved in the interactions abolished the dimerization. Overall, our structural, biochemical, and bioinformatics analyses provide a molecular basis for the binding of the NR4A2 protein dimers to NurREs and advance our understanding of the dimerization specificity of nuclear receptors.

PubMed: 31723028
DOI: 10.1074/jbc.RA119.010730

Experimental method

X-RAY DIFFRACTION (2.601 Å)