Abstract：
There are 48 nuclear receptors in the human genome, and many members of this superfamily have been implicated in human diseases. The NR4A nuclear receptor family consisting of three members, NR4A1, NR4A2, and NR4A3 (formerly annotated as Nur77, Nurr1, and NOR1, respectively), are still orphan receptors but exert pathological effects on immune-related and neurological diseases. We previously reported that prostaglandin A1 (PGA1) and prostaglandin A2 (PGA2) are potent activators of NR4A3, which bind directly to the ligand-binding domain (LBD) of the receptor. Recently, the co-crystallographic structures of NR4A2-LBD bound to PGA1 and PGA2 were reported, followed by reports of the neuroprotective effects of these possible endogenous ligands in mouse models of Parkinson\'s disease. Based on these structures, we modeled the binding structures of the other two members (NR4A1 and NR4A3) with these potential endogenous ligands using a template-based modeling method, and reviewed the similarity and diversity of ligand-binding mechanisms in the nuclear receptor family.
摘要：
人类基因组中有48个核受体,这个超家族的许多成员都与人类疾病有关。NR4A核受体家族由三个成员组成，NR4A1、NR4A2和NR4A3（以前分别注释为Nur77、Nurr1和NOR1），仍然是孤儿受体，但对免疫相关和神经系统疾病发挥病理作用。我们先前报道了前列腺素A1（PGA1）和前列腺素A2（PGA2）是NR4A3的有效激活剂，它们直接与受体的配体结合域（LBD）结合。最近,报道了与PGA1和PGA2结合的NR4A2-LBD的共晶结构，随后报道了这些可能的内源性配体在帕金森病小鼠模型中的神经保护作用。基于这些结构，我们使用基于模板的建模方法对其他两个成员（NR4A1和NR4A3）与这些潜在的内源性配体的结合结构进行建模，并综述了核受体家族中配体结合机制的相似性和多样性。
