Full-length nuclear receptor allosteric regulation.
Full-length nuclear receptor allosteric regulation.
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DOI：
10.1016/j.jlr.2023.100406
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发表时间：
2023-08
影响因子：
6.5
通讯作者：
Blind, Raymond D.
中科院分区：
文献类型：
--
作者：
Choi, Woong Jae;Haratipour, Zeinab;Blind, Raymond D.
关键词：
核受体是一个转录因子超家族，受多种脂类调节，包括磷脂、脂肪酸、基于血红素的代谢物和基于胆固醇的类固醇。核受体编码为典型的双域模块化转录因子，具有DNA结合域(DBD)和脂类配体结合域(LBD)，具有转录激活功能。几十年来对分离的核受体LBD的结构研究证实，脂-配体结合变构调节LBD的构象，调节转录辅助调节因子的招募，从而调节核受体的功能。这些结构研究有助于FDA批准的几种药物的开发，强调了了解脂质和核受体之间结构-功能关系的重要性。然而，关于全长核受体结构的已发表描述很少，关于脂类如何变构调节全长结构的描述就更少了。在这里，我们基于已发表的全长核受体结构来研究多结构域的相互作用，评估这些核受体中的结构域间界面作为脂类诱导变构调节位点的潜力。
Nuclear receptors are a superfamily of transcription factors regulated by a wide range of lipids that include phospholipids, fatty acids, heme-based metabolites, and cholesterol-based steroids. Encoded as classic two-domain modular transcription factors, nuclear receptors possess a DNA-binding domain (DBD) and a lipid ligand-binding domain (LBD) containing a transcriptional activation function. Decades of structural studies on the isolated LBDs of nuclear receptors established that lipid–ligand binding allosterically regulates the conformation of the LBD, regulating transcriptional coregulator recruitment and thus nuclear receptor function. These structural studies have aided the development of several FDA-approved drugs, highlighting the importance of understanding the structure-function relationships between lipids and nuclear receptors. However, there are few published descriptions of full-length nuclear receptor structure and even fewer descriptions of how lipids might allosterically regulate full-length structure. Here, we examine multidomain interactions based on the published full-length nuclear receptor structures, evaluating the potential of interdomain interfaces within these nuclear receptors to act as inducible sites of allosteric regulation by lipids.
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DOI：
10.1073/pnas.89.10.4653
发表时间：
1992-05-15
影响因子：
11.1
作者：
GOTTLICHER, M;WIDMARK, E;GUSTAFSSON, JA
通讯作者：
GUSTAFSSON, JA
影响因子：
5.8
作者：
Eargle, John;Luthey-Schulten, Zaida
通讯作者：
Luthey-Schulten, Zaida
影响因子：
5.4
作者：
Berger, Joel;Wagner, John A
通讯作者：
Wagner, John A
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
5.8
作者：
Flanagan, S. E.;Kapoor, R. R.;Ellard, S.
通讯作者：
Ellard, S.