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本文引用的文献

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Analysis of ligand binding and protein dynamics of human retinoid X receptor alpha ligand-binding domain by nuclear magnetic resonance.利用核磁共振分析人视黄酸X受体α配体结合域的配体结合与蛋白质动力学
Biochemistry. 2006 Feb 14;45(6):1629-39. doi: 10.1021/bi051474j.
2
Characterization of the interaction between retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators through structural and fluorescence anisotropy studies.通过结构和荧光各向异性研究对维甲酸受体/维甲酸X受体（RAR/RXR）异源二聚体与转录共激活因子之间的相互作用进行表征。
J Biol Chem. 2005 Jan 14;280(2):1625-33. doi: 10.1074/jbc.M409302200. Epub 2004 Nov 4.
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Allosteric control of ligand selectivity between estrogen receptors alpha and beta: implications for other nuclear receptors.雌激素受体α和β之间配体选择性的变构调控：对其他核受体的影响。
Mol Cell. 2004 Feb 13;13(3):317-27. doi: 10.1016/s1097-2765(04)00054-1.
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Quantitative NMR studies of high molecular weight proteins: application to domain orientation and ligand binding in the 723 residue enzyme malate synthase G.高分子量蛋白质的定量核磁共振研究：应用于723个残基的苹果酸合酶G的结构域取向和配体结合
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异二聚体伙伴RXRα对溶液中PPARγ激活功能-2螺旋的影响。

Effect of heterodimer partner RXRalpha on PPARgamma activation function-2 helix in solution.

作者信息

Lu Jianyun, Chen Minghe, Stanley Susan E, Li Ellen

机构信息

Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

出版信息

Biochem Biophys Res Commun. 2008 Jan 4;365(1):42-6. doi: 10.1016/j.bbrc.2007.10.143. Epub 2007 Oct 31.

DOI:10.1016/j.bbrc.2007.10.143
PMID:17980149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2170880/
Abstract

The structural mechanism of allosteric communication between retinoid X receptor (RXR) and its heterodimer partners remains controversial. As a first step towards addressing this question, we report a nuclear magnetic resonance (NMR) study on the GW1929-bound peroxisome proliferator-activated receptor gamma (PPARgamma) ligand-binding domain (LBD) with and without the 9-cis-retinoic acid (9cRA)-bound RXRalpha LBD. Sequence-specific 13C(alpha), 13C(beta), and 13CO resonance assignments have been established for over 95% of the 275 residues in the PPARgamma LBD monomer. The 1HN, 15N, and 13CO chemical shift perturbations induced by the RXRalpha LBD binding are located at not only the heterodimer interface that includes the C-terminal residue Y477 but also residues Y473 and K474 in the activation function-2 (AF-2) helix. This result suggests that 9cRA-bound RXRalpha can affect the PPARgamma AF-2 helix in solution and demonstrates that NMR is a powerful new tool for studying the mechanism of allosteric ligand activation in RXR heterodimers.

摘要

维甲酸X受体（RXR）与其异源二聚体伙伴之间变构通讯的结构机制仍存在争议。作为解决这个问题的第一步，我们报告了一项关于与GW1929结合的过氧化物酶体增殖物激活受体γ（PPARγ）配体结合域（LBD）的核磁共振（NMR）研究，该PPARγ LBD结合或未结合9-顺式视黄酸（9cRA）结合的RXRα LBD。已对PPARγ LBD单体中275个残基的95%以上建立了序列特异性的13C（α）、13C（β）和13CO共振归属。由RXRα LBD结合引起的1HN、15N和13CO化学位移扰动不仅位于包括C末端残基Y477的异源二聚体界面，还位于激活功能-2（AF-2）螺旋中的残基Y473和K474处。这一结果表明，9cRA结合的RXRα可以在溶液中影响PPARγ AF-2螺旋，并证明NMR是研究RXR异源二聚体中变构配体激活机制的强大新工具。