Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity.
Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity.
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类维生素A配体对RIP140的影响：与类维生素A受体的分子相互作用和生物活性。
DOI：
10.1021/bi020497k
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Wei,Li-Na
中科院分区：
文献类型：
--
作者：
Farooqui,Mariya;Franco,PeterJ;Thompson,Jim;Kagechika,Hiroyuki;Chandraratna,RoshanthaAS;Banaszak,Len;Wei,Li-Na
受体相互作用蛋白140(RIP140)与维甲酸受体(RAR)和维甲酸X受体(RXR)发生结构性相互作用，但激素结合增强了这种相互作用。配体非依赖性的相互作用是由RIP140的氨基和中心区介导的，而激动剂诱导的相互作用是由其包含一个新基序(1063RIP1076，−1076，LTKTNPILYMLQK)的羧基末端介导的。激动剂可轻微增强配体非依赖性相互作用，而RAR和RXR的配体依赖性相互作用均严格依赖于激动剂。在杂二聚体的背景下，RXR的配体占位对RIP140的分子相互作用和生物活性都起着更重要的作用。竞争和突变研究表明，1067Asn和1073Met在配体依赖的相互作用中起着重要作用。提出了一个模型来研究RIP140与RAR/RXR的结构性和激动剂依赖的相互作用。
Receptor interacting protein 140 (RIP140) interacts with retinoic acid receptor (RAR) and retinoid X receptor (RXR) constitutively, but hormone binding enhances this interaction. The ligand-independent interaction is mediated by the amino and central regions of RIP140 which contain a total of nine copies of the LXXLL motif, whereas the agonist-induced interaction is mediated by its carboxyl terminus which contains a novel motif (1063−1076, LTKTNPILYYMLQK). The ligand-independent interaction could be enhanced slightly by agonists, whereas the ligand-dependent interaction was strictly agonist dependent for both RAR and RXR. In the context of heterodimers, ligand occupancy of RXR played a more dominant role for both molecular interaction and biological activity of RIP140. Competition and mutation studies demonstrated an essential role for1067Asn and1073Met for a ligand-dependent interaction. A model was proposed to address the constitutive and agonist-dependent interaction of RIP140 with RAR/RXR.