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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biospotltesis in bacteria, plants, and mammalian cells
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The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biospotltesis in bacteria, plants, and mammalian cells

机译:神经递质受体锚蛋白gephyrin重建细菌,植物和哺乳动物细胞中的钼辅因子生物沉淀

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摘要

The molybdenum cofactor (Moco), a highly conserved pterin compound complexing molybdenum, is re- quired for the enzymatic activities of all molybdcnum enzymes except nitrogenase. Moco is synthesized by a unique and evolu. tionarily old pathway that requires the activities of at least six gene products. Some of the proteins involved in bacterial, plant and invertebrate Moco biosynthesis show striking homologies to the primary structure of gepbyrin, a polypeptide required for the clustering of inhibitory glycine receptors in postsynaptic mem- branes in the rat central nervous system. Hcre, we show that gephyrin binds with high affinity to molybdopterin, the meta- bolic precursor of Moco. Furthermore, gephyrin expression can reconstitute Moco biosynthesis in Moco-deficient bacteria, a molybdenum-dependent mouse cell line, and a Moco-deficient plant mutant. Conversely, inhibition of gephyrin expression by antisense RNA expression in cultured murine cells reduces their Moco content significantly. These data indicate that in addition to clustering glycine receptors, gepbyrin also is involved in Moco biosynthesis and illustrate the remarkable conservation of its function in Moco biosynthesis throughout phylogeny.
机译:钼辅助因子(Moco)是一种高度保守的蝶呤化合物,它与钼结合,要求除氮酶外的所有钼酶的酶促活性。 Moco由一种独特的进化方法合成。过去至少需要六个基因产物活动的途径。细菌,植物和无脊椎动物Moco生物合成中涉及的某些蛋白质与gepbyrin的一级结构表现出惊人的同源性,gepbyrin是大鼠中枢神经系统中突触后膜中抑制性甘氨酸受体聚集所需的多肽。从Hcre,我们证明了gephyrin与Moco的代谢前体Molybdopterin具有高亲和力。此外,gephyrin表达可以在Moco缺陷型细菌,钼依赖的小鼠细胞系和Moco缺陷型植物突变体中重建Moco的生物合成。相反地​​,在培养的鼠细胞中反义RNA表达对gephyrin表达的抑制显着降低了它们的Moco含量。这些数据表明,除聚簇甘氨酸受体外,gepbyrin还参与Moco生物合成,并说明了其在整个系统发育中在Moco生物合成中的功能显着保守。

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