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Evolution of alanine:glyoxylate aminotransferase intracellular targeting: structural and functional analysis of the guinea pig gene.

机译:丙氨酸:乙醛酸转氨酶细胞内靶向的演变:豚鼠基因的结构和功能分析。

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摘要

The distribution of alanine:glyoxylate aminotransferase 1 (AGT) within liver cells has changed many times during mammalian evolution. Depending on the particular species, AGT can be found in mitochondria or peroxisomes, or mitochondria and peroxisomes. In some cases significant cytosolic AGT is also present. In the livers of most rodents, AGT has what is thought to be the more 'ancestral' distribution (i.e. mitochondrial and peroxisomal). However, AGT is distributed very differently in the guinea pig, being peroxisomal and cytosolic. In this study, we have attempted to determine the molecular basis for the loss of mitochondrial AGT targeting and the apparent inefficiency of peroxisomal targeting of AGT in the guinea pig. Our results show that the former is owing to the evolutionary loss of the more 5' of two potential transcription and translation initiation sites, resulting in the loss of the ancestral N-terminal mitochondrial targeting sequence from the open reading frame. Guinea pig AGT is targeted to peroxisomes via the peroxisomal targeting sequence type 1 (PTS1) peroxisomal import machinery, even though its C-terminal tripeptide, HRL, deviates from the standard consensus PTS1 motif. Although HRL appears to target AGT to peroxisomes less efficiently than the classical PTS1 SKL, the main reason for the low efficiency of AGT peroxisomal targeting in guinea pig cells (compared with cells from other species) lies not with guinea pig AGT but with some other, as yet undefined, part of the guinea pig peroxisomal import machinery.
机译:在哺乳动物进化过程中,丙氨酸:乙醛酸转氨酶1(AGT)在肝细胞中的分布已发生了许多变化。根据特定的物种,AGT可以存在于线粒体或过氧化物酶体,或线粒体和过氧化物酶体中。在某些情况下,也存在明显的胞质AGT。在大多数啮齿动物的肝脏中,AGT具有更“祖传”的分布(即线粒体和过氧化物酶体)。但是,AGT在豚鼠中的分布非常不同,为过氧化物酶体和胞质。在这项研究中,我们试图确定豚鼠中线粒体AGT靶向丢失和过氧化物酶体靶向AGT明显无效的分子基础。我们的结果表明,前者是由于两个潜在的转录和翻译起始位点的更多5'的进化损失,导致开放阅读框的祖先N端线粒体靶向序列的损失。豚鼠AGT通过过氧化物酶体靶向序列1型(PTS1)过氧化物酶体导入机制靶向过氧化物酶体,即使其C端三肽HRL偏离标准的共有PTS1基序。尽管HRL似乎将AGT靶向过氧化物酶体的效率不如经典PTS1 SKL,但在豚鼠细胞(与其他物种的细胞相比)中,AGT过氧化物酶体靶向效率低的主要原因不是豚鼠AGT,而是其他一些,尚未定义,是豚鼠过氧化物酶体进口设备的一部分。

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