Targeting proteins to the glycosomes of African trypanosomes.
Targeting proteins to the glycosomes of African trypanosomes.
复制标题
将蛋白质靶向非洲锥虫的糖体。
DOI：
10.1146/annurev.mi.48.100194.000541
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发表时间：
1994
影响因子：
10.5
通讯作者：
Wang,CC
中科院分区：
文献类型：
--
作者：
Sommer,JM;Wang,CC
糖体是在属于动质体目的原生动物中发现的微体。这些高度特化的细胞器将通常位于其他真核细胞胞质溶胶中的大多数糖酵解酶区室化。最近在布氏锥虫中表达外源蛋白的成功已经允许对这些生物体中的糖体蛋白靶向信号进行详细分析。这些研究表明，先前鉴定的C-末端三肽过氧化物酶体靶向信号也在将蛋白质输入T.布鲁塞。然而，糖体和过氧化物酶体靶向信号在几个重要方面不同。糖体蛋白靶向的C-末端三肽序列要求相对宽松。在三个C末端氨基酸中，第一个可以是任何小的中性氨基酸;第二个应该能够形成氢键，而第三个是疏水氨基酸。这种简并的三肽序列显着不同，从更严格的要求观察到的蛋白质进口到哺乳动物过氧化物酶体，因此代表了一个机会，设计肽类似物，特异性地阻止糖体蛋白进口的一种可能的抗锥虫化疗。最近描述的N-末端信号，目标硫解酶的哺乳动物过氧化物酶体似乎没有功能，在进口到糖体。然而，已经在至少一种糖体蛋白中初步鉴定了一种新的内部靶向信号，其可以将报告蛋白靶向T.布鲁塞。糖体缺陷突变体最近已被分离出来，这将有助于鉴定参与糖体生物合成的基因。
Glycosomes are microbodies found in protozoa belonging to the order Kinetoplastida. These highly specialized organelles compartmentalize most of the glycolytic enzymes normally located in the cytosol of other eukaryotic cells. The recent success in expressing foreign proteins in Trypanosoma brucei has permitted a detailed analysis of glycosomal protein targeting signals in these organisms. These studies have revealed that the previously identified C-terminal tripeptide peroxisomal targeting signal also functions in the import of proteins into the glycosomes of T. brucei. However, the glycosomal and peroxisomal targeting signals differ in a few important ways. The C-terminal tripeptide sequence requirements for glycosomal protein targeting are comparatively relaxed. Of the three C-terminal amino acids, the first can be any small, neutral amino acid; the second should be capable of forming hydrogen bondings, whereas the third is a hydrophobic amino acid. This degenerate tripeptide sequence differs significantly from the more stringent requirements observed for the import of proteins into mammalian peroxisomes and thus represents an opportunity for designing peptide analogues that specifically block the glycosomal protein import for a possible antitrypanosomal chemotherapy. A recently described N-terminal signal that targets thiolase to the mammalian peroxisomes does not appear to function in import into the glycosomes. However, a novel internal targeting signal has tentatively been identified in at least one of the glycosomal proteins that can target a reporter protein to the glycosomes of T. brucei. Glycosome-deficient mutants have been isolated recently, which will aid in the identification of genes involved in the biogenesis of the glycosome.