Ligand-induced peroxisome proliferator-activated receptor alpha conformational change
Ligand-induced peroxisome proliferator-activated receptor alpha conformational change
复制标题
DOI：
10.1074/jbc.272.3.2013
复制
发表时间：
1997-01-17
影响因子：
4.8
通讯作者：
Leid, M
中科院分区：
文献类型：
--
作者：
Dowell, P;Peterson, VJ;Leid, M
在转染实验中，已经证明结构多样的过氧化物酶体增殖物和相关化合物诱导小鼠过氧化物酶体增殖物激活受体α（mPPAR α）的配体依赖性转录激活功能，测试其体外诱导mPPAR α内构象变化的能力。WY-14，643、5，8，11，14-二十碳四炔酸、LY-171883和氯贝酸均直接诱导mPPAR α构象变化，如差异蛋白酶敏感性测定所证明。羧基末端截短突变的mPPAR α差异影响这些配体诱导构象变化的能力，这表明，PPAR配体可能与受体的不同接触。过氧化物酶体增殖剂和相关化合物与mPPAR α的直接相互作用以及由此产生的mPPAR α构象改变可促进受体与转录中介因子和/或一般转录机制的相互作用，因此，可构成mPPAR α介导的配体依赖性转录激活的分子基础。
Structurally diverse peroxisome proliferators and related compounds that have been demonstrated to induce the ligand-dependent transcriptional activation function of mouse peroxisome proliferator activated receptor alpha (mPPAR alpha) in transfection experiments were tested for the ability to induce conformational changes within mPPAR alpha in vitro. WY-14,643, 5,8,11,14-eicosatetraynoic acid, LY-171883, and clofibric acid all directly induced mPPAR alpha conformational changes as evidenced by a differential protease sensitivity assay. Carboxyl-terminal truncation mutagenesis of mPPAR alpha differentially affected the ability of these ligands to induce conformational changes suggesting that PPAR ligands may make distinct contacts with the receptor. Direct interaction of peroxisome proliferators and related compounds with, and the resulting conformational alteration(s) in, mPPAR alpha may facilitate interaction of the receptor with transcriptional intermediary factors and/or the general transcription machinery and, thus, may underlie the molecular basis of ligand dependent transcriptional activation mediated by mPPAR alpha.