人类核受体RXR-ALPHA的配体结合域的载脂蛋白结构的重新审视版本

Jérôme Eberhardt, A. McEwen, W. Bourguet, D. Moras, A. Dejaegere
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引用次数: 5

摘要

视黄酮X受体(retinoic X receptor, RXR)在核受体(nuclear receptor, NRs)超家族中起着至关重要的作用,是几种核受体的强制性伴侣;因此,它作为转录因子的作用在许多信号传导途径中至关重要,如代谢、细胞发育、分化和细胞死亡。首次发表的RXRα载子配体结合域(apo - ligand-binding domain, LBD)结构,至今仍被用作参考,包含不准确性。在目前的工作中,使用现代晶体学工具纠正了这些不准确性。最重要的修正涉及螺旋H7中π-凸起的存在,它最初是作为一个规则的α-螺旋构建的。几个CHAPS分子的存在也被揭示出来,这些分子首次在电子密度图中可见,并稳定了包含螺旋H2的H1-H3环。载子RXR结构在破译NR配体的分子作用模式方面发挥了重要作用,目前仍在许多生物物理研究中使用。这种精细化的结构应该优先用于未来的解释实验以及载脂蛋白RXRα LBD的建模和结构动力学研究。
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A revisited version of the apo structure of the ligand-binding domain of the human nuclear receptor RXR-ALPHA
The retinoic X receptor (RXR) plays a crucial role in the superfamily of nuclear receptors (NRs) by acting as an obligatory partner of several nuclear receptors; its role as a transcription factor is thus critical in many signalling pathways, such as metabolism, cell development, differentiation and cellular death. The first published structure of the apo ligand-binding domain (LBD) of RXRα, which is still used as a reference today, contained inaccuracies. In the present work, these inaccuracies were corrected using modern crystallographic tools. The most important correction concerns the presence of a π-bulge in helix H7, which was originally built as a regular α-helix. The presence of several CHAPS molecules, which are visible for the first time in the electron-density map and which stabilize the H1–H3 loop, which contains helix H2, are also revealed. The apo RXR structure has played an essential role in deciphering the molecular mode of action of NR ligands and is still used in numerous biophysical studies. This refined structure should be used preferentially in the future in interpreting experiments as well as for modelling and structural dynamics studies of the apo RXRα LBD.
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期刊介绍: Acta Crystallographica Section F is a rapid structural biology communications journal. Articles on any aspect of structural biology, including structures determined using high-throughput methods or from iterative studies such as those used in the pharmaceutical industry, are welcomed by the journal. The journal offers the option of open access, and all communications benefit from unlimited free use of colour illustrations and no page charges. Authors are encouraged to submit multimedia content for publication with their articles. Acta Cryst. F has a dedicated online tool called publBio that is designed to make the preparation and submission of articles easier for authors.
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