Nuclear receptors homo sapiens Rev-erbbeta and Drosophila melanogaster E75 are thiolate-ligated heme proteins which undergo redox-mediated ligand switching and bind CO and NO.
Nuclear receptors homo sapiens Rev-erbbeta and Drosophila melanogaster E75 are thiolate-ligated heme proteins which undergo redox-mediated ligand switching and bind CO and NO.
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DOI：
10.1021/bi900697c
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发表时间：
2009-07-28
期刊：
影响因子：
2.9
通讯作者：
Burstyn, Judith N.
中科院分区：
文献类型：
--
作者：
Marvin, Katherine A.;Reinking, Jeffrey L.;Lee, Andrea J.;Pardee, Keith;Krause, Henry M.;Burstyn, Judith N.
核受体E75在D.调节人体昼夜节律的Rev-erbβ在其配体结合结构域（LBD）内结合血红素。用电子吸收光谱、MCD、共振拉曼光谱和EPR光谱研究了E75和Rev-erbβ的血红素配体结合结构域。这两种蛋白质进行氧化还原依赖性配体转换和CO和NO诱导的配体置换。在Fe（III）氧化态下，核受体血红素是低自旋的，并且与半胱氨酸（硫醇盐）6配位，作为两个轴向血红素配体之一。第六个配体是一个中性供体，可能是组氨酸。当血红素被还原为Fe（II）氧化态时，半胱氨酸（硫醇盐）被不同的中性供体配体取代，其身份未知。CO与E75（LBD）和Rev-erbβ（LBD）中的Fe（II）血红素结合，与第六个中性配体相对，可能是与Fe（III）状态中的第六个配体相同的组氨酸。NO与两种蛋白质的血红素结合;然而，NO-血红素在E75中为5-配位，在Rev-erbβ中为6-配位。这些核受体表现出与其他已知的氧化还原和气体传感器相似的配位特征，这表明E75和Rev-erbβ可能在细胞功能的血红素、氧化还原或气体调节控制中发挥作用。
Nuclear receptors E75, which regulates development in D. melanogaster, and Rev-erbβ, which regulates circadian rhythm in humans, bind heme within their ligand binding domains (LBD). The heme-bound ligand binding domains of E75 and Rev-erbβ were studied using electronic absorption, MCD, resonance Raman and EPR spectroscopies. Both proteins undergo redox-dependent ligand switching and CO- and NO-induced ligand displacement. In the Fe(III) oxidation state, the nuclear receptor hemes are low-spin and 6-coordinate with cysteine(thiolate) as one of the two axial heme ligands. The sixth ligand is a neutral donor, presumably histidine. When the heme is reduced to the Fe(II) oxidation state, the cysteine(thiolate) is replaced by a different neutral donor ligand, whose identity is not known. CO binds to the Fe(II) heme in both E75(LBD) and Rev-erbβ(LBD) opposite a sixth neutral ligand, plausibly the same histidine that served as the sixth ligand in the Fe(III) state. NO binds to the heme of both proteins; however, the NO-heme is 5-coordinate in E75 and 6-coordinate in Rev-erbβ. These nuclear receptors exhibit coordination characteristics that are similar to other known redox and gas sensors, suggesting that E75 and Rev-erbβ may function in heme-, redox- or gas-regulated control of cellular function.
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