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Crystal structures of YBHB and YBCL from Escherichia coli, two bacterialhomologues to a Raf kinase inhibitor protein

机译:大肠杆菌的YBHB和YBCL的晶体结构,与Raf激酶抑制剂蛋白的两个细菌同源物

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In rat and human cells, RKIP (previously known as PEEP) was characterized as an inhibitor of the MEK phosphorylation by Raf-l. In Escherichia coli, the genes ybhb and ybcl possibly encode two RKIP homologues while in the genomes of other bacteria and archaebacteria other homologous genes of RKIP have been found. The parallel between the cellular signaling mechanisms in eukaryotes and prokaryotes suggests that these bacterial proteins could be involved in the regulation of protein phosphorylation by kinases as well. We first showed that the proteins YBHB and YBCL were present in the cytoplasm and periplasm of E. coli, respectively, after which we determined their crystallographic structures. These structures verify that YBHB and YBCL belong to the same structural family as mammalian RKIP/PEBP proteins. The general fold and the anion binding site of these proteins are extremely well conserved between mammals and bacteria and suggest functional similarities. However, the bacterial proteins also exhibit some specific structural features, like a substrate binding pocket formed by the dimerization interface and the absence of cis peptide bonds. This structural variety should correspond to the recognition of multiple cellular partners.
机译:在大鼠和人类细胞中,RKIP(以前称为PEEP)被表征为Raf-1对MEK磷酸化的抑制剂。在大肠杆菌中,基因ybhb和ybcl可能编码两个RKIP同源物,而在其他细菌和古细菌的基因组中,已经发现RKIP的其他同源基因。真核生物和原核生物中细胞信号传导机制之间的相似性表明,这些细菌蛋白质也可能参与激酶对蛋白质磷酸化的调节。我们首先表明,蛋白质YBHB和YBCL分别存在于大肠杆菌的细胞质和周质中,之后我们确定了它们的晶体结构。这些结构证明YBHB和YBCL与哺乳动物RKIP / PEBP蛋白属于同一结构家族。这些蛋白质的一般折叠和阴离子结合位点在哺乳动物和细菌之间极为保守,并提示功能相似。但是,细菌蛋白还表现出某些特定的结构特征,例如由二聚化界面形成的底物结合袋和不存在顺式肽键。这种结构上的变化应对应于多个细胞伴侣的识别。

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