MEMBRANE TOPOLOGY OF THE MAMMALIAN P450-CYTOCHROMES
MEMBRANE TOPOLOGY OF THE MAMMALIAN P450-CYTOCHROMES
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DOI：
10.1096/fasebj.6.2.1537456
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发表时间：
1992-01-06
期刊：
影响因子：
4.8
通讯作者：
BLACK, SD
中科院分区：
文献类型：
--
作者：
BLACK, SD
哺乳动物P450细胞色素的膜拓扑结构已被广泛应用于计算、蛋白质分解、化学修饰、基因工程和免疫化学等方面的研究。内质网细胞色素的初步结果似乎表明，一种多面体、四到八个跨膜锚定模型，其活性部位埋在膜中。然而，最近的发现表明，微粒体P450只通过位于NH2末端的一到两个跨膜肽与内质网结合，并且活性部位是一个大的细胞质结构域的一部分，该结构域可能有一个或两个额外的外周膜接触。膜结合的状态被认为是相当坚硬的，并且血红素的平面位于与内质网平面垂直和平行之间。线粒体P450细胞色素在成熟时缺乏疏水的NH2末端，因此在这一方面与微粒体同工酶不同。然而，尽管线粒体膜内细胞色素P450的确切拓扑结构仍有待阐明，但某些特征显然与微粒体P450的特征相似。因此，P450基因超家族的膜拓扑可能遵循类似的模式。
The membrane topology of the mammalian P450 cytochromes has been studied intensively by computational approaches, proteolysis, chemical modification, genetic engineering, and immunochemistry. Initial results for the cytochromes of the endoplasmic reticulum appeared to indicate a polytopic, four to eight transmembrane anchor model with an active site buried in the membrane. However, recent findings show that the microsomal P450s are bound to the endoplasmic reticulum by only one or two transmembrane peptides located at the NH2-terminal end, and that the active site is part of a large cytoplasmic domain that may have one or two additional peripheral membrane contacts. The membrane-bound state is viewed as rather rigid, and the plane of the heme lies between perpendicular and parallel to the plane of the endoplasmic reticulum. The mitochondrial P450 cytochromes lack a hydrophobic NH2 terminus in the mature form, and thus differ from the microsomal isozymes in this significant way. However, although the exact topology of cytochrome P450 in the inner mitochondrial membrane remains to be elucidated, certain features are clearly comparable to those of microsomal P450. Therefore, the membrane topology of the P450 gene superfamily may follow a similar pattern.