A Saccharomyces cerevisiae homolog of the human adrenoleukodystrophy transporter is a heterodimer of two half ATP-binding cassette transporters.
A Saccharomyces cerevisiae homolog of the human adrenoleukodystrophy transporter is a heterodimer of two half ATP-binding cassette transporters.
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DOI：
10.1073/pnas.93.21.11901
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发表时间：
1996-10
影响因子：
11.1
通讯作者：
N. Shani;David Valle
中科院分区：
文献类型：
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作者：
N. Shani;David Valle
肾上腺脑白质营养不良蛋白(ALDP)和70 kDa过氧化物体膜蛋白(PMP70)是人过氧化体膜上的半ATP结合盒(ABC)转运蛋白。ALDP和PMP70具有相同的序列同源性，都与遗传性疾病有关。PXA1和YKL741是酿酒酵母基因，编码ALDP和PMP70的同源物。Pxa1p被认为是ALDP的同源基因，参与了脂肪酸的过氧化体β氧化，而YKL741是酵母基因组测序项目发现的一个开放阅读框。在这里，我们指定YKL741为PXA2，并表明其蛋白产物Pxa2p和Pxa1p一样，与过氧化物体相关，但不是组装所必需的。携带PXA1、PXA2或两者的基因破坏的酵母菌株具有相似的表型，在后者的情况下，非加性表型。我们还发现，Pxa1p的稳定性在没有Pxa2p的情况下显著降低。最后，我们发现Pxa1p和Pxa2p共免疫沉淀。这些遗传和物理数据表明，Pxa1p和Pxa2p异源二聚体形成一个完整的过氧体ABC转运体，参与脂肪酸的β-氧化。这一结果预测在哺乳动物的过氧化物体膜中存在类似的异二聚体ABC转运蛋白。
The adrenoleukodystrophy protein (ALDP) and the 70-kDa peroxisomal membrane protein (PMP70) are half ATP-binding cassette (ABC) transporters in the human peroxisome membrane. ALDP and PMP70 share sequence homology and both are implicated in genetic diseases. PXA1 and YKL741 are Saccharomyces cerevisiae genes that encode homologs of ALDP and PMP70. Pxa1p, a putative ortholog of ALDP, is involved in peroxisomal beta-oxidation of fatty acids while YKL741 is an open reading frame found by the yeast genome sequencing project. Here we designate YKL741 as PXA2 and show that its protein product, Pxa2p, like Pxa1p, is associated with peroxisomes but not required for their assembly. Yeast strains carrying gene disruption of PXA1, PXA2, or both have similar and, in the case of the latter, nonadditive phenotypes. We also find that the stability of Pxa1p, but not Pxa2p, is markedly reduced in the absence of the other. Finally, we find that Pxa1p and Pxa2p coimmuno-precipitate. These genetic and physical data suggest that Pxa1p and Pxa2p heterodimerize to form a complete peroxisomal ABC transporter involved in fatty acid beta-oxidation. This result predicts the presence of similar heterodimeric ABC transporters in the mammalian peroxisome membrane.