Both coactivator LXXLL motif-dependent and -independent interactions are required for peroxisome proliferator-activated receptor γ (PPARγ) function
Both coactivator LXXLL motif-dependent and -independent interactions are required for peroxisome proliferator-activated receptor γ (PPARγ) function
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DOI：
10.1074/jbc.275.6.3733
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发表时间：
2000-02-11
影响因子：
4.8
通讯作者：
Zhou, GC
中科院分区：
文献类型：
--
作者：
Chen, SY;Johnson, BA;Zhou, GC
核受体激活依赖于辅激活因子的募集，包括CREB结合蛋白（GBP/p300）和类固醇受体辅激活因子-1（SRC-1），使用三维NMR方法来探测过氧化物酶体增殖物激活受体γ中的辅激活因子结合界面。在CBP肽的存在下，对应于LED的螺旋3、4、5和12中的20个残基的峰被减弱。丙氨酸突变体显示，M301 A，V315 A，Y320 A，L468 A和E471 A是CBP和SRC-1结合以及基于细胞的转录所必需的。在螺旋4的PPAR γ LBD的几个额外的氨基酸是有缺陷的CBP招聘，但保留相对正常的SRC-1招聘。因此，这些氨基酸残基可能是核受体LED与离散辅激活分子相互作用的特异性的重要决定因素。
Nuclear receptor activation is dependent on recruitment of coactivators, including CREB-binding protein (GBP/p300) and steroid receptor coactivator-1 (SRC-1), A three-dimensional NMR approach was used to probe the coactivator binding interface in the peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand binding domain (LBD), In the presence of a CBP peptide, peaks corresponding to 20 residues in helices 3, 4, 5, and 12 of the LED were attenuated. Alanine mutants revealed that M301A, V315A, Y320A, L468A, and E471A were required for binding of both CBP and SRC-1 and for cell-based transcription. Several additional amino acids in helix 4 of the PPAR gamma LBD were defective with respect to CBP recruitment, but retained relatively normal SRC-1 recruitment. Thus these amino acid residues may be important determinants of specificity for nuclear receptor LED interactions with discrete coactivator molecules.