6lc1
Structural basis of NR4A1 bound to the human pituitary proopiomelanocortin gene promoter
Structural highlights
FunctionNR4A1_HUMAN Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2.[1] Publication Abstract from PubMedThe 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 A 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. Structural basis of NR4A1 bound to the human pituitary proopiomelanocortin gene promoter.,Jiang L, Wei H, Yan N, Dai S, Li J, Qu L, Chen X, Guo M, Chen Z, Chen Y Biochem Biophys Res Commun. 2019 Dec 7. pii: S0006-291X(19)32320-4. doi:, 10.1016/j.bbrc.2019.11.192. PMID:31822342[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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