A steroid receptor coactivator acts as the DNA-binding partner of the methoprene-tolerant protein in regulating juvenile hormone response genes.

A steroid receptor coactivator acts as the DNA-binding partner of the methoprene-tolerant protein in regulating juvenile hormone response genes.
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DOI:
10.1016/j.mce.2014.06.021
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发表时间:
2014-08-25
影响因子:
4.1
通讯作者:
Zhu J
Zhu J
中科院分区:
医学2区
文献类型:
--
作者:
Li M;Liu P;Wiley JD;Ojani R;Bevan DR;Li J;Zhu J

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甲氧普仑耐受蛋白(Methoprene-tolerant protein,Met)是昆虫体内的保幼激素(juvenile hormone,JH)受体。JH结合的Met与βFtz-F1相互作用的类固醇受体辅激活因子(FISC)形成复合物,它们一起调节蚊子中的JH反应基因。这两种蛋白质都含有碱性螺旋环螺旋(bHLH)和PAS基序。在这里,我们证明了FISC是Met与JH反应元件(JHRE)结合的强制性伴侣。单独的Met或FISC不能结合先前表征的JHRE,而Met-FISC复合物的形成对于结合JHRE是必要的且足够的。这种结合需要Met和FISC的DNA结合结构域的参与。Met和FISC识别的最佳DNA序列包含一个核心共有序列GCACGTG。虽然蚊子细胞中的Met-FISC复合物的形成是由JH诱导的,但细菌表达的Met和FISC的异二聚化和DNA结合是JH独立的,这意味着需要额外的蚊子蛋白来调节受体复合物的形成。
Methoprene-tolerant (Met) protein is a juvenile hormone (JH) receptor in insects. JH-bound Met forms a complex with the βFtz-F1-interacting steroid receptor coactivator (FISC) and together they regulate JH response genes in mosquitoes. Both proteins contain basic-helix-loop-helix (bHLH) and PAS motifs. Here we demonstrated that FISC is the obligatory partner of Met for binding to JH-response elements (JHREs). Met or FISC alone could not bind a previously characterized JHRE, while formation of the Met-FISC complex was necessary and sufficient to bind to the JHRE. This binding required participation of the DNA-binding domains of both Met and FISC. The optimal DNA sequence recognized by Met and FISC contained a core consensus sequence GCACGTG. While formation of the Met-FISC complex in mosquito cells was induced by JH, heterodimerization and DNA binding of bacterially expressed Met and FISC were JH-independent, implying that additional mosquito proteins were required to modulate formation of the receptor complex.
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