核受体
转录因子
受体
神经元源性孤儿受体1
配体(生物化学)
结合位点
抄写(语言学)
细胞生物学
小异二聚体伴侣
功能(生物学)
化学
计算生物学
小分子
兴奋剂
生物
生物化学
基因
语言学
哲学
作者
Zhong Lin Wang,Benoît Galand,Jinsong Liu,Srividya Prasad,Piia Aarnisalo,Xiaohong Liu,Haoda Xu,Nigel Walker,Thomas Perlmann
出处
期刊:Nature
[Springer Nature]
日期:2003-05-01
卷期号:423 (6939): 555-560
被引量:525
摘要
Members of the nuclear receptor (NR) superfamily of transcription factors modulate gene transcription in response to small lipophilic molecules. Transcriptional activity is regulated by ligands binding to the carboxy-terminal ligand-binding domains (LBDs) of cognate NRs. A subgroup of NRs referred to as 'orphan receptors' lack identified ligands, however, raising issues about the function of their LBDs. Here we report the crystal structure of the LBD of the orphan receptor Nurr1 at 2.2 A resolution. The Nurr1 LBD adopts a canonical protein fold resembling that of agonist-bound, transcriptionally active LBDs in NRs, but the structure has two distinctive features. First, the Nurr1 LBD contains no cavity as a result of the tight packing of side chains from several bulky hydrophobic residues in the region normally occupied by ligands. Second, Nurr1 lacks a 'classical' binding site for coactivators. Despite these differences, the Nurr1 LBD can be regulated in mammalian cells. Notably, transcriptional activity is correlated with the Nurr1 LBD adopting a more stable conformation. Our findings highlight a unique structural class of NRs and define a model for ligand-independent NR function.
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